The antidepressant vortioxetine is primarily metabolised by the polymorphic enzyme CYP2D6. The objective of this study was to investigate the effect of CYP2D6 genotype on exposure and therapeutic failure of vortioxetine. The analysis included data from CYP2D6-genotyped patients (N=458) on vortioxetine treatment from a Norwegian therapeutic drug monitoring database. Compared with CYP2D6 normal metabolizers (NMs; N=242), vortioxetine exposure was 3.0-fold (p<0.001) increased in poor metabolizers (PMs; N=35), 1.5-fold (p<0.001) increased in intermediate metabolizers (IMs; N=173), and not significantly changed (p=0.21) in ultra-rapid metabolizers (UMs; N=8). Compared with NMs, treatment switch from vortioxetine to alternative antidepressants was 8.0-fold (95%CI: 2.0-32.3, p=0.001) more frequent among PMs and 12.7-fold (95%CI: 1.1-94.9, p=0.02) more frequent among the CYP2D6 UMs. In conclusion, CYP2D6 genotype was associated with significant changes in vortioxetine exposure and may also be associated with risk of therapeutic failure.

There is growing evidence that the clinical manifestations of COVID-19 are not just respiratory, but also gastrointestinal symptoms. The difference of organ infection should be considered. In addition, as a key molecule mediating viral infection of cells, angiotensin-converting enzyme 2 (ACE2) provides an important intervention means for the exploration of antivirus. This is particularly important as the pandemic intensifies.

Background and Purpose: There is an increasing number of evidence-based indications for pharmacogenetic (PGx) tests and a growing demand for PGx screening. We aimed to evaluate clinical relevance of a 16-gene panel test for PGx-guided pharmacotherapy. Experimental Approach: Observational cohort study of subjects tested with a PGx panel for variants of ABCB1, COMT, CYP1A2, CYP2B6, CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, CYP4F2, DPYD, OPRM1, POR, SLCO1B1, TPMT and VKORC1. Specialized clinical pharmacology consultations with PGx-guided pharmacotherapy management were supported by the PGx expert system SONOGEN XP. Study outcomes were PGx-based changes and recommendations regarding current and potential future medication. Key Results: PGx-testing was triggered by specific drug-gene pairs in 102 subjects, whereas screening was performed in 33. Based on PHARMGKB expert guidelines the 16-gene panel identified at least one “actionable” variant relevant for current or potential future medication in all 135 (100%) tested patients. Drugs that triggered PGx-testing were clopidogrel in 60, tamoxifen in 15, polypsychopharmacotherapy in 9, opioids in 7, and other in 11 patients. Among those, PGx variants resulted in clinical recommendations to change PGx-triggering drugs in 33 (32.4 %), and other current pharmacotherapy in 23 (22.5%). Conclusion and Implications: The 16-gene PGx panel detected clinically relevant variants in a high proportion of tested patients, and SONOGEN XP supported their interpretation based on latest evidence. Additional costs of panel vs. single gene tests are moderate, and the efficiency of PGx panel testing challenges traditional cost-benefit calculations for single drug-gene pairs. However, PGx-guided pharmacotherapy requires specialized consultations with interdisciplinary collaborations.

Aim：Chronic subdural hematoma (CSDH) is common in aged people, and minimally invasive surgical interventions such as burr-hole-drainage and twist-drill craniostomy are the first-line therapeutic options for this condition. However, the mortality rate among super-aged patients (over 90 years of age) with CSDH is as high as 38.4% after these surgical procedures. Atorvastatin alone or in combination with dexamethasone has been proven to be effective in eliminating CSDH. In the current study, the researchers evaluated the therapeutic efficacy of atorvastatin with or without dexamethasone on the CSDH patients over 90 years. Methods：The study attempted to treat 12 super-aged patients with primary or post-operative relapsed CSDH by using atorvastatin alone or in combination with dexamethasone. The changes in hematoma volume measured with computed tomography (CT) or magnetic resonance imaging (MRI) and the patients’ neurological improvement were monitored by activities of daily living (ADL) and modified Rankin scale (MRS) scores. Results：Treatment with atorvastatin or atorvastatin combined with low-dose dexamethasone had beneficial effects on hematoma elimination and/or symptom remission within 6 to 24 weeks in 12 super-aged patients. All of them showed complete recovery after 1~4 years of follow-up. Conclusion：The findings in this study indicate that atorvastatin with or without dexamethasone is safe and effective for the treatment for CSDH in super-aged patients.

Obesity and non-alcoholic fatty liver disease (NAFLD) are “lifestyle diseases” related to harmful habits, affecting a large portion of the global population at a steadily increasing prevalence. These disorders are inextricably associated with each other and therapeutic lifestyle changes (TLC) remain the cornerstone of their management. Nevertheless, TLC are difficult to achieve or maintain, and the use of medicines is often suggested. Different categories of medicines have been proposed, many of which are not officially licensed for these conditions. For NAFLD in particular, no drug with official indication exists so far. Thus, it is important that clinicians are aware of the quality of evidence supporting the efficacy of drugs before a decision to treat. To assist rational medical decision, in the present systematic review, we sought to evaluate the quality of evidence from phase III/IV clinical trials of major drugs currently proposed for obesity and NAFLD.

Aim. Polypharmacy may increase the prevalence of potential multidrug interactions (pMDIs), where one drug interacts with two or more other drugs, possibly amplifying the risk of a potential adverse drug event (pADE). The major goal of this study was to estimate the prevalence of amplifying pMDIs in an ambulatory cohort of older patients. Methods. Current medication lists of 22033 randomly chosen outpatients ≥50 years old were extracted from the New York Presbyterian Hospital (NYP) data warehouse. Network analysis identified patients prescribed three or more interacting drugs from their current medication lists. Potentially harmful interactions were identified from the NYP drug-drug interaction alerting system. pMDIs were considered amplifying if the interactions increased the probability of a pADE through pharmacokinetic, pharmacodynamic or conditional mechanisms. Results. pMDIs were identified in 5.1% of the medication lists; 3.4% were three-drug and 1.1% were four-drug pMDIs. The most common drugs involved were psychotropic, comprising 23.3% of the total drugs. The most common pADEs associated with the interactions were serotonin syndrome (17.2%), seizures (14.4%), prolonged QT interval (15.8%) and bleeding (14.4%). pADE amplification risk was identified in 71.8% of three-drug pMDIs when one drug interacted with two others, 97.8% when all three interacted with each other, and 93% for four-drug pMDIs. Conclusion. Our data suggest that approximately 5% of elderly ambulatory patients may be exposed to pMDIs which amplify the probability of associated adverse drug events. The recent and persistent rise in polypharmacy will likely increase the prevalence of pMDIs and potential exposure to serious adverse events.

Second-generation H1-antihistamines are generally considered to be safe. Here we describe a healthy boy who developed left-arm convulsions after repeated exposure to a dry suspension of desloratadine combined with Huatengzi granules. The boy had no family or disease history of epilepsy, convulsions, or any other drug therapy. The Naranjo Adverse Drug Reaction Probability Scale was used to determine that the convulsions were probably related to desloratadine. Our findings suggest that desloratadine (a second-generation H1-antihistamine) can cause epileptic convulsions in healthy children, and so clinicians should be vigilant of the possibility of central side effects.

With the changes of the times and the growth of public demand for medical services, the service objects, service contents and service approaches of hospital pharmacists are also changing and increasing. By summarizing the changes of hospital pharmacists' practice in hospitals and their contributions to the improvement of hospital service quality in the practice of hospital pharmaceutical care, this paper hopes that more doctors, nurses and patients can have a more in-depth understanding of the specific work of pharmacists, which, at the same time, will also provide some reference for pharmacists at home and abroad to optimize the level of pharmaceutical care. Compared with doctors and nurses, hospital pharmacists have a much more systematic and professional drug knowledge system and service concept, which can guarantee that they can undertake the responsibilities of rational use of drugs, control of medical expenditure, guarantee of efficacy, reduction of medical risks, reduction of doctors' workload, improvement of national health and so on. After years of practice and research, pharmacists have gradually realized their own value and established professional needs through hospital pharmaceutical care.

Coronaviruses (CoVs) are a large family of viruses responsible for the severe ill effects on human health. The most severe outbreak includes Severe Acute Respiratory Syndrome (SARS-CoV), Middle East Respiratory Syndrome (MERS-CoV) and Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 poses major challenges to clinical management because no specific FDA-approved therapy yet to be available. Thus, the existing therapies are being used for the treatment of COVID-19, which are under clinical trials and compassionate use, based on in vitro and in silico studies. In this review, we summarized the potential therapies like small molecules, bioactive compounds, nucleoside and nucleotide analogs, peptides, antibodies, natural products, and synthetic compounds targeting the complex molecular interactions involved in COVID-19. In this review＞230 natural and chemically synthesized drug therapies were described with their recent advances in research and development being done in terms of their chemical, structural and functional properties. Further, provided insights on possible targets for viral cells, viral proteins, viral replication, and different molecular pathways for the discovery of novel viral- and host-based therapeutic targets against SARS-CoV-2.

Granulocyte colony stimulating factor (G-CSF) has been widely used as a mobilizing agent to rapidly increase peripheral blood stem and progenitor cells. Limited data is available for G-CSF-associated late-onset coronary thrombosis and thrombocytosis. We report a case of a 23-year-old Chinese Han patient who presented with acute myocardial infarction and thrombocytosis after finishing bone marrow harvesting and peripheral blood stem cell collection following G-CSF treatment several days later. By using antiplatelet drugs and undergoing percutaneous transluminal coronary angioplasty, the patient’s symptoms were relieved and his platelet level decreased to normal. This is the first suspected case report of late-onset coronary thrombosis and thrombocytosis related to G-CSF. Caution should be taken for the delayed adverse reactions in patients undergoing G-CSF mobilizing.

Background and purpose: Osteoarthritis (OA) is a chronic and progressive joint disorder characterized by structural damage to one or more joints. However, drugs that could cure or at least stop the progression of this disease are still given no satisfactory outcome. The purpose of this work is to study the potential OA disease-modifying effects of atorvastatin in an experimental model of osteoarthritis and the possible underlining mechanisms if any. Experimental Approach: Seventy-six adult male Sprague-Dawley rats (250-300gms) were used throughout this study. Forty rats were used to assess the effect of atorvastatin in surgically induced OA. While 36 rats were used to assess its anti-inflammatory effect in carrageenan-induced paw edema. In the model of OA; the degree of joint stiffness was assessed by measuring the angle of knee extension besides, the histopathological changes of the OA knee joints and measurement of serum Interleukin-1beta (IL-1β), Matrix metalloproteinase-13 (MMP13), and reduced glutathione (GSH) concentration were biochemically assessed. In the carrageenan-induced paw edema, the paw thickness and pain threshold were assessed in different groups. Key Results: Atorvastatin was found to produce significant improvement of joint stiffness, the histopathological changes, a significant correction in the increased MMP13 and IL1-β, and the decreased GTH in OA rats. Also, atorvastatin showed a significant improvement in both paw thickness and pain threshold. Conclusion and Implications These results present atorvastatin as OA disease-modifying drug worse clinical trials.

COVID-19 pandemic has badly affected the world, having fatality rate ranging from 1 to 10% that differs in various countries. The median time from symptoms to clinical recovery is 6–8 weeks and to death is 2 to 8 weeks. Severity of disease and increasing mortality in COVID 19 is primarily due to presence of comorbidities like cardiovascular disease, pre-existing lungs disease, hypertension, diabetes, obesity and cancer. It is already known to us that humans show difference in drug responses because of their varied genetic make-up. Population genomics furnish an insight about genetic characteristic of a populations and it is critical in determining susceptibility, severity and natural protection against infectious diseases. Therefore, understanding the population genetic makeup may be deemed necessary to identify those who are at risk or protective from disease and develop genomics information, that would be useful in providing insight about COVID‐19 disease severity or outcomes. Some of the proposed genetic gateways in COVID 19 pathogenesis are mentioned in this review including roles of ACE2 gene, HLA gene, Chromosome 3P21.31, ABO locus, genes responsible for cytokine storm, TLR-pathway, Family Mediterranean fever and G6PD deficiency. Significant interindividual variability in response to drug therapy exists in patients. This review also evaluates the current therapeutics in COVID-19 like hydroxycholoroquine, azithromycin, RNA polymerase inhibitors, interleukin inhibitors, antivirals, ivermectin, doxycyclin and their pharmacogenomics viewpoint. Such Pharmacogenomic studies are very helpful for the physicians to choose and give accurate first line therapy for COVID 19 patients.

Abstract Aim To evaluate the clinical and humanistic patient outcomes of a community pharmacy (CP) Minor Ailment Service (MAS) compared to usual pharmacist care (UC). Methods A cluster randomised controlled trial was conducted over six months in CP. The pharmacist-patient intervention consisted of a standardised consultation on a web-based program using co-developed protocols pharmacists’ training, practice change facilitators and patients’ educational material. Patients were followed up ten days after initial consultation. Primary outcomes were appropriate medical referral and changes to direct product request. Secondary outcomes were symptom resolution, reconsultation rates for the same ailment and health related quality of life (HRQoL). Results A total of 808 patients were recruited by 27 CP (323 MAS and 485 UC). Patients visiting MAS pharmacies had higher odds for being referred to the general practitioner (OR=2.343, CI95%=[1.146-4.792]); a higher increase in HRQoL (OR=1.026, CI95%=[1.002-1.051]) and higher number of reconsultation (OR=1.833, CI95%=[1.151-2.919]) compared to UC. No significant differences were observed for symptom resolution and modification of treatments with direct product requests. Conclusions Patients with minor ailments are triaged and managed in a safe and effective way in CP, facilitating appropriate self-selection of non-prescription medicines. MAS reinforce pharmacists’ involvement with patient engagement.

Background: Pregnancy significantly increases the need for iron. The prevalence of anemia in pregnant women is high, affecting 41.8% of all pregnant women worldwide. In patients with low tolerance to oral iron, it is recommended to start them on parenteral iron therapy but with variable degree of efficacy. Hence this meta-analysis was done with the following aim. Aim: This study aims to assess the efficacy of various iron preparations in pregnant women with Iron deficiency anemia (IDA). Methods: Randomised controlled trials (RCTs) (available as full free text) which included iron therapy in pregnant women with iron deficiency anemia were retrieved from electronic databases viz. PubMed, Google scholar and IndMed, with specific search terms. Qualities of RCTs were assessed using JADAD score and four RCTs with high score were included for analysis using RevMan 5.3 software. Outcome measures were change in hemoglobin levels and serum ferritin concentration after one month of therapy. Results: In the four RCTs included, a total of 267 patients were treated with oral iron and 267 patients were treated with parenteral iron therapy. Change in the hemoglobin levels between the 2 groups had a standard mean difference of 0.73, 95% CI (-0.05-1.52), with the p-value of 0.07. To assess the change in the serum ferritin concentration a total of 188 patients in oral iron and 197 patients in parenteral iron therapy were included. There was a standard mean difference of 0.88, 95% CI (0.60-1.66), with a p-value of <0.00001.

Background: Community pharmacy services have evolved to include medical and pharmaceutical interventions alongside dispensing. Whilst established pharmacogenomic (PGx) testing is available throughout the Netherlands, this is primarily based in hospital environments and for specialist medicines. Aim: The aim of this work was to describe how best to implement PGx services within community pharmacy, considering potential barriers and enablers to service delivery and how to address them. Method: The service was implemented across a selection of community pharmacies in the Netherlands. Data was captured on test outcomes and through a pharmacist survey. Results: Following testing, 17.8% of the clinical samples were recommended to avoid certain medication (based on their current medicines use), and 14.0% to have their dose adjusted. Pre-emptive analysis of genotyped patients showed that the majority (99.2%) had actionable variants. Pharmacists felt confident in their operational knowledge to deliver the service, but less so in applying that knowledge. Delivering the service was believed to improve relationships with other healthcare professionals. Conclusion: These results add to the evidence in understanding how PGx can be delivered effectively within the community pharmacy environment. Training pharmacists in how to respond to patient queries and make clinical recommendations may enhance service provision further.

SARS-CoV-2 infections are the most contagious among the three coronavirus infections the world has witnessed till date which have affected almost all parts of the world in millions of population till date since its outbreak in china in Dec. 2019. Moreover, it has severely hit the world economy and therefore there is a dire need to develop the treatment of this deadly disease. Numbers of potential vaccines are in the early or advanced stage of clinical trials. But the development of a vaccine is a very tedious and time consuming task. Therefore, numbers of groups are working on the repurposing of drugs with already known safety and efficacy profile to shorten the time of development of the potential treatment. The main aim of this review article is to summarize the clinical outcomes of the various drugs which have been repurposed for the treatment of COVID-19 associated with SARS-CoV-2.

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Background: Rivaroxaban is an oral anticoagulant used widely for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). During long-term anticoagulant therapy, delayed or missed doses are common. However, a lack of practical instructions on remedial methods has created a barrier to maximise the benefit of the medications. This study aimed to explore appropriate remedial dosing regimens for non-adherent rivaroxaban-treated patients. Methods: Monte Carlo simulation based on a previously established rivaroxaban population pharmacokinetic/pharmacodynamic (PK/PD) model for patients with NVAF was employed to design remedial dosing regimens. The proposed regimens were compared with remedial strategies in the European Heart Rhythm Association (EHRA) guide by assessing deviation time in terms of drug concentration, factor Xa activity, and prothrombin time under various scenarios of non-adherence. Results: The proposed remedial dosing regimens were dependent on delay duration. The missed dose should be taken immediately when the delay does not exceed 6 h; a half dose is advisable when the delay is between 6-20 h. A missed dose should be skipped if less than 4 h remains before the next dose. Age or renal function does not significantly influence remedial dosing regimens. The proposed regimens resulted in shorter deviation time than that of the EHRA guide in most non-adherence scenarios. Conclusion: EHRA guide may not provide optimal remedial strategies for rivaroxaban-treated non-adherent patients based on simulation. PK/PD and simulation provide valid evidence on the remedial dosing regimen of rivaroxaban for patients with NVAF, which could help to minimise the risk of bleeding and thromboembolism.

Fixed drug eruption (FDE) is a common type of cutaneous adverse drug reaction. It is a delayed-type of hypersensitivity reaction that occurs and recurs as lesions at the same skin site due to repeated intake of an offending drug. Drugs like ciprofloxacin, acetaminophen, fluconazole, nimesulide, and metronidazole have been reported to cause the bullous form of FDE. FDE due to azithromycin have been reported, but the bullous variant is extremely rare. We herewith describe a case of azithromycin‑induced bullous FDE; which is, to the best of our knowledge, the second such case being reported.

Pharmacovigilance (PV) deals with the detection, collection, assessment, understanding and prevention of adverse effects associated with the drugs. The objective of PV is to ensure safety of the medicines and patients by monitoring and reporting of all adverse drug reactions (ADRs) associated with prescribed medicine usage. Findings have indicated that about 0.2-24% of hospitalization cases are due to ADRs out of which 3.7% of patients have lethal ADRs. The reasons includes number of prescribing drugs, increased new drugs in the market, and inadequate PV system for ADRs monitoring, lack of awareness and knowledge about ADRs reporting. Serious ADRs leads to enhanced hospital stay, increased treatment cost, risk of death, and many medical and economic consequences. Therefore, ADR reporting at its first instance is important to avoid further harmful effects of the prescribed drugs. In India, the rate of ADR reporting is less than 1% whereas worldwide it is 5% due to lack of awareness about PV and ADR monitoring among healthcare providers and patients. Spontaneous reporting is the most commonly used PV method to report ADRs in both urban and rural areas of India. Evidences revealed that there is not any effective ADR reporting mechanisms developed in rural areas causing underreporting of ADR thus increasing threat to the rural population. Hence, PV and ADR reporting awareness among healthcare professionals and patients, telecommunication, telemedicine, use of social media and electronic medical records, and artificial intelligence are the potential approaches for prevention, monitoring and reporting of ADR in rural areas.

Background; Osteoporosis is one of such disease which causes bone mass reduction by decreased formation of new bones. Low bone mineral density is frequent factor for osteoporosis. Increased osteoclast life span and advanced osteocytes as well as osteoblasts apoptosis is well adopted pathophysiological mechanism for low bone mass. Women are more prone than man. Approximately 200 million women have osteoporosis worldwide. Objective; Therefore, this study is designed to compare efficacy of bisphosphonates and recombinant human Para-thyroid hormone in treatment of osteoporosis. Main outcome measures; The comparison of these two treatment strategies is based upon therapeutic effectiveness, cost of therapy and availability of the drugs. Methods; The total duration of study was 1 year and during the study period a total 60 samples were analyzed randomly. Data was collected using a well-designed questionnaire. Results; rhPTH increase bone mass density (BMD) by 8-9% while bisphosphonates and estrogen therapy increase BMD 3-5% during the same time period. Conclusion; The current study was conducted in local population so that we could offer them the test possible treatment among the two most common treatment therapies available for osteoporosis.

Objective: To study the safety and pharmacokinetic (PK) profile of S-oxiracetam (S-ORT) in healthy volunteers, so as to provide a safe and reasonable basis for the application of formulation in phase II clinical programs. Methods: In part 1, subjects were intravenously administered single-ascending dose (2.0-8.0g) S-ORT. In part 2, subjects were treated by two-sequence, two-period crossover design. In part 3, subjects were intravenously injected with 4.0 g S-ORT once a day for 7 days. The biological samples were collected to evaluate the PK parameters and urine excretion rate. The safety profile of the drug was also evaluated throughout the test process. Results: Only 1 subject displayed a mild AE (adverse event) without obvious dosage-related AE, and SAE (serious adverse event). Within the range of 2.0-8.0 g for a single dose, Cmax, AUC0-t, and AUC0-∞ increased with an increase of dosage. The urine excretion rate of the prototype drug was approximately 60%. The consecutive administration of drug could not cause a substantial accumulation of S-ORT. The plasma drug concentration-time curves for both S-ORT and R-oxiracetam (R-ORT) were found to be almost identical. Conclusions: The safety, tolerance and PK characteristics of S-ORT in the healthy volunteers within a range of 2.0-8.0 g for a single dose, or with 4.0 g for 7 consecutive days were found to be acceptable. The pharmacokinetics of S-ORT and racemic oxiracetam (ORT) were observed to be basically the same. The injection of S-ORT can be used at once-a-day dosing regimen for Phase II clinical studies.

Cinnamon is herbal medicine supposed to improve metabolic disorder of PCOS. This study investigated the effects of cinnamon extract effect on insulin resistance, metabolic factors, and menstrual cyclicity for woman with PCOS. This is systematic review and meta-analysis of randomized controlled trials (RCTs). We searched the MEDLINE, Cochrane, Google Scholar, and Pubmed databases to identify relevant studies using cinnamon extract for PCOS. Five RCTs consisting 206 women were entered in the meta-analysis. Significant differences in body mass index (mean difference (MD) = -0.21, 95% CI:-1.80 to 1.38, p=0.79; 143 participants), weight (MD = 1.08, 95% CI: -2.79 to 4.96, p=0.58; 143 participants), insulin resistance (MD = -0.19, 95% CI: -0.54 to 0.15, p=0.27, 190 participants), fasting blood glucose (MD= -4.8, 95% CI: -8.04 to -1.57, p=0.004; 143 participants), trygliceride (MD= -10.73, 95%CI: -26.35 to 4.88, p=0.18; 143 participants), LDL-cholesterol (MD=-3.39, 95% CI: -12.27 to 5.50, p=0.46; 143 participants), HDL-cholesterol (MD= -27.24 , 95%CI : -32.62 to -21.85, p< 0.00001; 143 participants), total cholesterol (MD= -7.8, 95% CI: -17.48 to 1.89, p=0.11; 143 participants), insulin (MD = -2.20, 95% CI: -4.17 to -0.23, p=0.03; 143 participants), DHEA level (MD = -0.1, 95% CI: -0.62 to 0.41, p=0.70; 104 participants), and menstrual cyclicity in 6 months (MD= 2.28, 95% CI: 1.83 to 2.73, p< 0.00001; 33 participants) were obtained. Cinnamon can be a potential supplementary therapy agent for PCOS women as it improves fasting blood glucose, insulin level, HDL–cholesterol and menstrual cyclicity in PCOS women.

Background and purpose: Paclitaxel is a widely used anti-neoplastic agent but has low oral bioavailability due to gut extrusion by P-glycoprotein (P-gp). Oral paclitaxel could be more convenient, less resource intensive, and more tolerable than intravenous administration. Encequidar (HM30181A) is a novel, minimally absorbed gut specific P-gp inhibitor. We tested whether administration of oral paclitaxel with encequidar (oPac+E) achieved comparable AUC to intravenous paclitaxel (IVP) 80mg/m2. Experimental approach: We conducted a multi-centre randomised crossover study with two treatment periods. Patients (pts) with advanced cancer received either oral paclitaxel 615mg/m2 divided over three days and encequidar 15mg orally one-hour prior, followed by IVP 80mg/m2, or the reverse sequence. PK blood samples were taken up to day 9 for oPac+E and day 5 for IVP. Key Results: 42 pts were enrolled; 35 completed both treatment periods. AUC0-∞was 5033.5 +/- 1401.1 ng.h/mL for oPac+E and 5595.9 +/- 1264.1 ng.h/mL with IVP. The geometric mean ratio (GMR) for AUC was 89.5% (90% CI 83.9-95.5). Mean absolute bioavailability of oPac+E was 12%. PK parameters did not change meaningfully after 4 weeks administration of oPac+E in an extension study. G3 treatment emergent adverse events occurred in 7 (18%) pts with oPac+E and 2 (5%) with IVP. 75% of pts preferred oPac+E over IVP. Conclusion and Implications: GMR for AUC was within the predefined acceptable range of 80%-125% for demonstrating equivalence. oPac+E is tolerable and there is no evidence of P-gp induction with repeat administration. With further study, oPac+E is a candidate to replace IVP.