An 83 year old man had an acute attack of gout. He treated himself with colchicine drops (2 mg in two days) and received diclofenac because of continuous pain. Concurrently he had muscle weakness in his limbs. Four days later he became immobile and was transferred to hospital with flaccid tetraparesis (British Medical Research Council grade II-III). He had no signs of infection, hepatic or rena...

P-glycoprotein is an efflux transporter located in the blood-brain barrier. (R)-[11C]Verapamil is widely used as a PET tracer to investigate its function in patients with epilepsy, Alzheimer's disease, and other neurodegenerative diseases. Currently it is not possible to use this successful tracer in clinics without a cyclotron, because of the short half-life of carbon-11. We developed two new ...

The calcium antagonist verapamil (a mixture of D-and L-racemers) is a potent modulator of the multi-drug resistance phenotype in vitro at a concentration of 6 gM. Clinical studies have shown dose-limiting toxicity of hypotension and heart block when plasma levels approach the concentrations active in vitro. Previous data indicate that the D-isomer is less cardioactive than the L-isomer but they...

Some mechanism-based inhibitors cause irreversible inhibition by forming a metabolic intermediate complex (MIC) with cytochrome P450. In the present study, 54 molecules (substrates of CYP3A and amine-containing compounds that are not known substrates of CYP3A) were spectrophotometrically assessed for their propensity to cause MIC formation with recombinant CYP3A4 ( b5). Comparisons of common ph...

Urine drug testing is used in many applications, including preemployment screening, human performance testing, neonatal care, probation monitoring, and emergency room care. Rapid, cost-effective immunochemical techniques such as enzyme immunoassays are effective tools for excluding the presence of various drugs; however, they may lack the specificity necessary for accurate identification. Confi...

Calcium-channel blockers are known to affect slow inward current in a frequencydependent fashion. The purpose of these experiments was to study use-dependent effects of verapamil, diltiazem, and nifedipine on atrioventricular conduction in vivo. Loading and maintenance infusion techniques were developed to study each drug at a series of stable plasma concentrations in autonomically blocked dogs...

P-glycoprotein (P-gp) is a major efflux transporter contributing to the efflux of a range of xenobiotic compounds at the bloodbrain barrier (BBB). In the present study, we evaluated the P-gp function at the BBB using positron emission tomography (PET) in nonhuman primates. Serial brain PET scans were obtained in three rhesus monkeys after intravenous administration of [C]verapamil under control...