Rhabdomyolysis in association with simvastatin and amiodarone.

Objective: To report a case of severe myopathy associated with concomitant simvastatin and amiodarone therapy.

Case Summary: A 63-year-old white man with underlying insulin-dependent diabetes, recent coronary artery bypass surgery, and postoperative hemiplegia was treated with aspirin, metoprolol, furosemide, nitroglycerin, and simvastatin. Due to recurrent atrial fibrillation, oral anticoagulation with phenprocoumon and antiarrhythmic treatment with amiodarone were initiated.

Effect of St John's wort on the activities of CYP1A2, CYP3A4, CYP2D6, N-acetyltransferase 2, and xanthine oxidase in healthy males and females.

Aims: To investigate the influence of St. John's wort (SJW) on CYP3A4, CYP1A2, CYP2D6, N-acetyltransferase 2 (NAT2), and xanthine oxidase (XO) activities in healthy males and females.

Methods: Eight males and eight females were treated with SJW extract (3 x 300 mg day(-1)) for 14 days.

Appropriateness of serum level determinations of antiepileptic drugs.

Aim: To assess the appropriateness of the determination of the serum levels of the antiepileptic drugs (AEDs) phenytoin, valproic acid and carbamazepine in inpatients of a tertiary care institution.

Methods: We performed a retrospective analysis of 602 AED serum level determinations. Appropriateness criteria regarding indication and timing were defined a priori using existing criteria from the literature.

Determination of -3858G-->A and -164C-->A genetic polymorphisms of CYP1A2 in blood and saliva by rapid allelic discrimination: large difference in the prevalence of the -3858G-->A mutation between Caucasians and Asians.

Introduction: Two mutations in CYP1A2, -164C-->A (allele CYP1A2*F) and -3858G-->A (allele CYP1A2*C), affecting the inducibility of the enzyme, have been published. The aim of this study was to develop a high throughput allelic discrimination assay for these mutations in both saliva and blood and to determine their frequency in Caucasians.

Methods: An allelic discrimination assay, based on the fluorogenic 5'-nuclease activity (TaqMan), was developed for the two mutations.

Reduced hepatic glycogen stores in patients with liver cirrhosis.

Background: Patients with alcoholic liver cirrhosis have reduced hepatic glycogen stores but the mechanisms leading to this finding are not clear.

Methods: We therefore determined the hepatic glycogen content in patients with alcoholic (n = 9) or biliary cirrhosis (n = 8), and in control patients undergoing liver surgery (n = 14). All patients were in the postabsorptive state.

Interaction of ibuprofen and probenecid with drug metabolizing enzyme phenotyping procedures using caffeine as the probe drug.

Aims: To examine the suspected inhibitory potential of the over-the-counter (OTC) drug ibuprofen on N-acetyltransferase 2 (NAT2) in vitro and in vivo and the possible implications for phenotyping procedures using caffeine as probe drug.

Methods: We first studied the inhibitory effect of ibuprofen on NAT2 in vitro, using human liver cytosol and sulfamethazine as substrate. In vivo 15 fast and 15 slow acetylating healthy volunteers were treated with a single dose of ibuprofen (800 mg) orally and phenotyped for NAT2, CYP1A2, and xanthine oxidase (XO) with caffeine as probe drug before and during drug treatment.

Determination of carnitine and acylcarnitines in urine by high-performance liquid chromatography-electrospray ionization ion trap tandem mass spectrometry.

A high-performance liquid chromatography-mass spectrometry method has been developed for the simultaneous determination of native carnitine and eight acylcarnitines in urine. The procedure uses a solid-phase extraction on a cation-exchange column and the separation is performed without derivatization within 17 min on a reversed-phase C8 column in the presence of a volatile ion-pairing reagent. The detector was an ion trap mass spectrometer and quantification was carried out in the MS-MS mode.

Mechanisms of liver steatosis in rats with systemic carnitine deficiency due to treatment with trimethylhydraziniumpropionate.

Rats with systemic carnitine deficiency induced by treatment with trimethylhydraziniumpropionate (THP) develop liver steatosis. This study aims to investigate the mechanisms leading to steatosis in THP-induced carnitine deficiency. Rats were treated with THP (20 mg/100 g) for 3 or 6 weeks and were studied after starvation for 24 h.

Appropriateness of digoxin level monitoring.

Aim: To evaluate the proportion of inappropriate digoxin level determinations.

Methods: We performed a retrospective analysis of 210 randomly selected digoxin plasma level determinations in inpatients. Appropriateness criteria were defined combining existing criteria from the literature.

Fulminant liver failure associated with clarithromycin.

Objective: To report a patient developing fulminant liver failure while being treated with clarithromycin for pneumonia.

Case Summary: A 58-year-old white woman developed fulminant liver failure while being treated with the macrolide antibiotic clarithromycin for pneumonia. Comedication included N-acetylcysteine, atenolol, and isradipine.

Association between body mass index and liver disorders: an epidemiological study.

Background/aims: Cross-sectional studies showed an association between obesity and liver disorders. Information on incidence rates from epidemiological studies is scarce.

Methods: To explore the association between body mass index (BMI) and incident liver disorders, we conducted a follow-up study with a nested case-control analysis using the UK-based General Practice Research Database.

Impaired ketogenesis is a major mechanism for disturbed hepatic fatty acid metabolism in rats with long-term cholestasis and after relief of biliary obstruction.

Background/aims: Rats with long-term cholestasis have reduced ketosis of unknown origin.

Methods: Fatty acid metabolism was studied in starved rats with biliary obstruction for 4 weeks (bile duct ligated rats = BDL rats), and 3, 7, 14, 28 and 84 days after reversal of biliary obstruction by Roux-en-Y anastomosis (RY rats), and in sham-operated control rats.

Results: BDL rats had reduced beta-hydroxybutyrate concentrations in plasma (0.

Fatal drug interaction between cholestyramine and phenprocoumon.

We describe a patient with a prosthetic aortic valve who developed fatal valve thrombosis due to an interaction between phenprocoumon and cholestyramine. The general practitioner who had prescribed cholestyramine was aware of a potential interaction between these two drugs and the patient ingested cholestyramine exactly according to the rules of the manufacturer (>1 h before phenprocoumon). However, due to enterohepatic cycling and the long half-life of phenprocoumon, an interaction between these two drugs could not be avoided.

Tolterodine-associated acute mixed liver injury.

Objective: To report a patient with an acute mixed liver injury associated with tolterodine therapy.

Case Summary: An 81-year-old white woman with urge incontinence experienced malaise, fever, and gastrointestinal disturbances 18 days after starting tolterodine 2 mg twice daily. The patient's concurrent medications included flunitrazepam, diclofenac, and dorzolamide/timolol eye drops.

Long-term administration of L-carnitine to humans: effect on skeletal muscle carnitine content and physical performance.

Background: Long-term administration of high oral doses of L-carnitine on the skeletal muscle composition and the physical performance has not been studied in humans.

Methods: Eight healthy male adults were treated with 2 x 2 g of L-carnitine per day for 3 months. Muscle biopsies and exercise tests were performed before, immediately after, and 2 months after the treatment.

Hepatic and skeletal muscle glycogen metabolism in rats with short-term cholestasis.

Background/aims: To study the effect of short-term cholestasis on glycogen metabolism.

Methods: Rats were bile duct ligated (BDL) for 4 or 8 days and compared to sham-operated control rats pair-fed to BDL (pair-fed CON) or fed ad libitum (ad libitum-fed CON).

Results: Four days after surgery, the hepatic glycogen content was 21.