Effect of rifampin on the pharmacokinetics and pharmacodynamics of gliclazide

Objective Our objective was to investigate the effect of rifampin (INN, rifampicin) on the pharmacokinetics and pharmacodynamics of gliclazide, a sulfonylurea antidiabetic drug. Method In a randomized 2‐way crossover study with a 4‐week washout period, 9 healthy Korean subjects were treated once dai...

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Published in:Clinical pharmacology and therapeutics 2003-10, Vol.74 (4), p.334-340
Main Authors: Park, Ji‐Young, Kim, Kyoung‐Ah, Park, Pil‐Whan, Park, Chan‐Woong, Shin, Jae‐Gook
Format: Article
Language:English
Subjects:
Adult
Antibacterial agents
Antibiotics, Antitubercular - pharmacology
Antibiotics. Antiinfectious agents. Antiparasitic agents
Area Under Curve
Biological and medical sciences
Blood Glucose - drug effects
Cross-Over Studies
Drug Interactions
General and cellular metabolism. Vitamins
Gliclazide - blood
Gliclazide - pharmacokinetics
Gliclazide - pharmacology
Half-Life
Humans
Hypoglycemic Agents - blood
Hypoglycemic Agents - pharmacokinetics
Hypoglycemic Agents - pharmacology
Insulin - blood
Male
Medical sciences
Metabolic Clearance Rate
Pharmacology. Drug treatments
Rifampin - pharmacology
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Summary:Objective Our objective was to investigate the effect of rifampin (INN, rifampicin) on the pharmacokinetics and pharmacodynamics of gliclazide, a sulfonylurea antidiabetic drug. Method In a randomized 2‐way crossover study with a 4‐week washout period, 9 healthy Korean subjects were treated once daily for 6 days with 600 mg rifampin or with placebo. On day 7, a single dose of 80 mg gliclazide was administered orally. Plasma gliclazide, blood glucose, and insulin concentrations were measured. Results Rifampin decreased the mean area under the plasma concentration–time curve for gliclazide by 70% (P < .001) and the mean elimination half‐life from 9.5 to 3.3 hours (P < .05). The apparent oral clearance of gliclazide increased about 4‐fold after rifampin treatment (P < .001). A significant difference in the blood glucose response to gliclazide was observed between the placebo and rifampin phases. Conclusion The effect of rifampin on the pharmacokinetics and pharmacodynamics of gliclazide suggests that rifampin affects the disposition of gliclazide in humans, possibly by the induction of cytochrome P450 2C9. Concomitant use of rifampin with gliclazide can considerably reduce the glucose‐lowering effects of gliclazide. Clinical Pharmacology & Therapeutics (2003) 74, 334–340; doi: 10.1016/S0009‐9236(03)00221‐2
ISSN:0009-9236
1532-6535
DOI:10.1016/S0009-9236(03)00221-2