Candesartan Has No Clinically Meaningful Effect on the Plasma Concentrations of Cytochrome P450 2C8 Substrate Repaglinide in Humans.

In vitro evidence shows that the acyl--D-glucuronide metabolite of candesartan inhibits cytochrome P450 (CYP) 2C8 with an inhibition constant of 7.12 M. We investigated the effect of candesartan on the plasma concentrations and glucose-lowering effect of repaglinide, a sensitive clinical CYP2C8 index substrate.

Experiences from the initial 3 years of introducing the British Pharmacological Society and UK Medical Schools Council Prescribing Safety Assessment for Danish junior doctors.

Aims: The British Pharmacological Society and UK Medical Schools Council Prescription Safety Assessment (BPS/MSC PSA) is an electronic platform developed for assessing the prescription skills of medical students. Our aim was to investigate the feasibility of the BPS/MSC PSA in addressing prescribing competencies among junior doctors in a hospital setting.

Methods: The Department of Clinical Pharmacology at Odense University Hospital established a Danish translated programme using the BPS/MSC PSA platform.

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Intrauterine hormonal contraception devices are widely used among Danish women. Cases of breast cancer have been reported in women using the devices and studies have found evidence of an increased risk, but a new meta-analysis did not find an increased risk. The reported relative risks in some of the studies are numerically substantial as quoted in this review, but it is very important that physicians take absolute numbers into account when interpreting risk in order to provide the best guidance of patients with regard to contraception and associated risks.

Neurofilament light chain as a biomarker of axonal damage in sensory neurons and paclitaxel-induced peripheral neuropathy in patients with ovarian cancer.

Paclitaxel-induced peripheral neuropathy (PIPN) is a barrier to effective cancer treatment and impacts quality of life among patients with cancer. We used a translational approach to assess the utility of neurofilament light chain (NFL) as a biomarker of PIPN in a human cell model and in patients with ovarian cancer. We measured NFL in medium from human induced pluripotent stem cell-derived sensory neurons (iPSC-SNs) exposed to paclitaxel.

DPYD genotyping and dihydropyrimidine dehydrogenase (DPD) phenotyping in clinical oncology. A clinically focused minireview.

Background: In clinical oncology, systemic 5-fluorouracil (5-FU) and its oral pro-drugs are used to treat a broad group of solid tumours. Patients with dihydropyrimidine dehydrogenase (DPD) enzyme deficiency are at elevated risk of toxicity if treated with standard doses of 5-FU. DPYD genotyping and measurements of plasma uracil concentration (DPD phenotyping) can be applied as tests for DPD deficiency.

No significant influence of OCT1 genotypes on the pharmacokinetics of morphine in adult surgical patients.

We investigated the impact of genetic variants in OCT1 (SLC22A1) on morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) pharmacokinetics in adult patients scheduled for major surgery. Blood samples were taken before and 5, 10, 15, 30, 45, 60 and 90 min after a bolus of morphine (0.15 mg/kg).

Drug-drug cross contamination in the Swisslog fully automated medication handling system.

Objective: The risk of drug-drug cross contamination in drug dispensing robots in hospital pharmacies causes cumbersome restraints to be put on the production of the robot for example by scheduling high-risk drugs to be dispensed at the end of the day. However, we were unable to find published data on the matter, and therefore performed a worst-case scenario study to assess the magnitude of the problem.

Methods: We measured dexamethasone residue left on the suction cup after the production of 100 and 400 dexamethasone tablets, and after 20 paracetamol tablets used as a negative control.

Four phase 1 trials to evaluate the safety and pharmacokinetic profile of single and repeated dosing of SCO-101 in adult male and female volunteers.

SCO-101 (Endovion) was discontinued 20 years ago as a new drug under development against sickle cell anaemia. Data from the phase 1 studies remained unpublished. New data indicate that SCO-101 might be efficacious as add-on therapy in cancer.

A phase I study of the PARP inhibitor niraparib in combination with bevacizumab in platinum-sensitive epithelial ovarian cancer: NSGO AVANOVA1/ENGOT-OV24.

Background: Combining poly(ADP-ribose) polymerase (PARP) inhibitors with antiangiogenic agents appeared to enhance activity vs PARP inhibitors alone in a randomized phase II trial.

Materials And Methods: In AVANOVA (NCT02354131) part 1, patients with measurable/evaluable high-grade serous/endometrioid platinum-sensitive ovarian cancer received bevacizumab 15 mg/kg every 21 days with escalating doses of niraparib capsules (100, 200, or 300 mg daily) in a 3 + 3 dose-escalation design. Primary objectives were to evaluate safety and tolerability and to determine the recommended phase II dose (RP2D).

Progression-free survival in oncology: Caveat emptor!

Overall survival (OS) is the undisputed gold standard efficacy end-point in cancer drug trials. It is with growing concern that we observe how progression-free survival (PFS) gains ground as surrogate end-point in its place. PFS has appeal because it is resource-efficient, but it has severe shortcomings.

Clinical Pharmacokinetics of Paclitaxel Monotherapy: An Updated Literature Review.

Paclitaxel is an anticancer agent efficacious in the treatment of ovarian, breast, and lung cancer. Due to a strong link between the pharmacokinetics and therapeutic efficacy of paclitaxel, we reviewed the literature on paclitaxel pharmacokinetics. Systematic data mining was performed to extract the maximum concentration (C ), clearance (CL), and time of paclitaxel plasma concentration above 0.

The Pharmacogenetics of Tacrolimus in Corticosteroid-Sparse Pediatric and Adult Kidney Transplant Recipients.

Introduction: Tacrolimus is a calcineurin inhibitor used as an immunosuppressant drug in solid organ transplantation, and is mainly metabolized by cytochrome P450 (CYP) 3A4 and CYP3A5. Studies have shown an association between the CYP3A5 genotype and tacrolimus dose-adjusted trough concentrations. Variants in the genes PPARA, POR and CYP3A4 have recently been shown to influence tacrolimus metabolism.

[Lactic acidosis in a 24-year-old woman with status asthmaticus].

A 24-year-old woman with asthma presented with symptoms of upper airway infection and tachypnoea and wheezes. She had a history of admissions to intensive care units (ICU) due to respiratory insufficiency. The initial lactate concentration was 2.

A Cancer That Went Up in Smoke: Pulmonary Reaction to e-Cigarettes Imitating Metastatic Cancer.

e-Cigarettes have gained worldwide popularity as a substitute for smoking, but concern has been raised regarding the long-term effects associated with their use. We report a case of a 45-year-old female consumer of e-cigarettes who presented with 4 months of abdominal pain and fever. Initial imaging discovered multiple pulmonary nodules and liver lesions suspicious of widespread metastases; however, an extensive evaluation found no evidence of malignancy.

Neurotoxicity and low paclitaxel clearance associated with concomitant clopidogrel therapy in a 60-year-old Caucasian woman with ovarian carcinoma.

Aim: The aim of the present case report was to describe a novel pharmacokinetic drug–drug interaction between the antiplatelet agent clopidogrel and the antineoplastic agent paclitaxel.

Methods: The patient was identified in a previously described cohort of 93 patients with ovarian carcinoma treated with paclitaxel. The effect of clopidogrel acyl-β-D-glucuronide on the metabolism of paclitaxel was assessed in human liver microsomes.

Exploratory study of total and free prednisolone plasma exposure and cushingoid appearance, quality of life and biochemical toxicity in adult male kidney transplant recipients.

Background And Objective: Long-term adverse effects of oral glucocorticoids are frequent and serious. Large between-patient variability in the pharmacokinetics of prednisolone might explain why drug dose is a poor predictor of drug-related toxicity. The aim of the study was to investigate relationships between prednisolone exposure and adverse effects.