Avtor/Urednik		Rozman, Blaž
Naslov		Clinical pharmacokinetics of leflunomide
Tip		članek
Vir		Clin Pharmacokinet
Vol. in št.		Letnik 41, št. 6
Leto izdaje		2002
Obseg		str. 421-30
Jezik		eng
Abstrakt		Leflunomide is the first disease-modifying antirheumatic drug to be approved for rheumatoid arthritis in the past 10 years. Orally administered leflunomide is almost completely converted into its active metabolite A77 1726 (hereafter referred to as M 1). M 1 displays linear pharmacokinetics at the dosages of leflunomide used in clinical practice. It has a long elimination half-life (approximately 2 weeks), reaching a steady state after approximately 20 weeks. M1 is highly bound to plasma proteins. The pharmacokinetics of M1 are not affected by food intake, and dosage requirements are not influenced by age or gender. Approximately 90% of a single dose of leflunomide is eliminated, 43% in urine, primarily as leflunomide glucuronides and an oxalinic acid derivative of M1, and 48% in faeces, primarily as Ml. Elimination can be dramatically increased by using charcoal or cholestyramine. In vitro studies have shown no major influence of leflunomide on the metabolism of analgesics, nonsteroidal anti-inflammatory drugs and methotrexate, drugs usually used in the treatment of rheumatoid arthritis. In clinical studies with a limited number of patients using these drugs concomitantly, no safety problems appeared. Nonspecific inducers of cytochrome P450 (CYP) and some drugs metabolised by CYP2C9 affect the metabolism of M1, and caution should be used in patients corelated with them. Additional in vitro and in vivp pharmacokinetic studies are needed to better understand the nonenzymatic and enzymatic metabolism of leflunomide. Addictional clinical trials should be performed in order to find new indications for leflunomide in rheumatic arhritis. This review is a summary of current knowledge of the pharmacokinetics of leflunomide, focusing primarily on humans and n particular on patients woth rheumatoid arthritis.
Deskriptorji		ARTHRITIS, RHEUMATOID ANTIRHEUMATIC AGENTS BIOTRANSFORMATION INTESTINAL ABSORPTION BIOLOGICAL AVAILABILITY DRUG INTERACTIONS