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No effect of garlic extract on saquinavir kinetics and hepatic CYP3A4 function measured by the erythromycin breath test
Author(s) -
Jacek H.,
Rentsch K. M.,
Steinert H. C.,
PauliMagnus C.,
Meier P. J.,
Fattinger K.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.304
Subject(s) - saquinavir , cyp3a4 , medicine , pharmacology , midazolam , erythromycin , chemistry , gastroenterology , antibiotics , biochemistry , metabolism , immunology , cytochrome p450 , human immunodeficiency virus (hiv) , sedation , viral load , antiretroviral therapy
Background Garlic extracts are widely used as herbal supplements. Garlic extract intake markedly decreased plasma concentrations of the CYP3A4 substrate saquinavir in 6 out of 9 volunteers (Clin Infect Dis 2002;34:234). Furthermore, high doses of garlic induced hepatic CYP3A1 expression and function in rats (J Agric Food Chem 2002;50:378). Therefore we studied the effects of garlic extract on hepatic CYP3A4 function as measured by erythromycin breath test. Methods Ten male healthy volunteers participated in a cross‐over study. Two study periods were separated by three weeks of garlic extract intake (Garlipure 1200mg/d). In each period, volunteers underwent an erythromycin breath test and repeated blood samples after a single dose of 1200mg saquinavir. Results The erythromycin breath test was comparable prior to and after three weeks of garlic extract intake with means(SD) of 2.3(0.3) and 2.2(0.4) and a geometric mean (95%CI) ratio of garlic vs. baseline of 96(93,107)%. Saquinavir AUC decreased in 7 and increased in 3 volunteers with means(SD) of 1.9(0.6) and 1.7(0.9)h.ug/l. and a geometric mean (95%CI) ratio of 86(74,136)%. Conclusions Our results indicate that the usual dose of garlic extract for 3 weeks does not change the function of hepatic CYP3A4 and does not alter saquinavir exposures after an oral single dose. These results are in line with resent studies reporting no effects of garlic on the urinary OH‐midazolam/midazolam ratio and on alprazolam kinetics. Clinical Pharmacology & Therapeutics (2004) 75 , P80–P80; doi: 10.1016/j.clpt.2003.11.304