title: Effect of diallyl trisulfide on the pharmacokinetics of nifedipine in rats.
abstract: This study aimed to evaluate the effect of diallyl trisulfide (DATS), a major component derived from garlic, on the pharmacokinetics of nifedipine. Pharmacokinetic parameters of nifedipine were determined in rats following an oral gavage (3 mg/kg) or intravenous administration (0.75 mg/kg) of nifedipine with co-administration of DATS (20 mg/kg) and long-term pretreatment of DATS (20 mg/kg/d for 15 consecutive days). Compared to the control groups, higher C(max) and AUC(0-24 h) were observed for oral gavage of nifedipine after short-term and long-term pretreatment of DATS, whereas those for intravenous nifedipine were little changed. The oral bioavailabilities of nifedipine were remarkably enhanced via the concomitant use of DATS. In conclusion, DATS increased the oral exposure of nifedipine in rats likely by the modification of intestinal metabolism of nifedipine, indicating that combined use of DATS or DATS-containing supplement with nifedipine may require caution because high plasma concentrations may lead to an undesired toxicity of this agent. Practical Application: Patients suffering from cardiovascular disease should take caution in combined use of DATS or DATS-rich garlic supplement with nifedipine because long-term treatment of DATS could lead high plasma concentrations of nifedipine.
authors.affiliation: Dept. of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical Univ., Mailbox 32#, 103 Wenhua Rd., Shenyang 110016, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Mei-Juan
authors.initials: MJ
authors.lastname: Zou
authors.forename: Nan
authors.initials: N
authors.lastname: Zhao
authors.forename: Jun-Gang
authors.initials: JG
authors.lastname: Ren
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.forename: Gang
authors.initials: G
authors.lastname: Cheng
mesh_terms: D000498:Allyl Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D001682:Biological Availability; D002121:Calcium Channel Blockers / Q000097:blood / Q000493:pharmacokinetics*; D019587:Dietary Supplements / Q000009:adverse effects*; D018565:Food-Drug Interactions; D005737:Garlic / Q000737:chemistry; D006207:Half-Life; D008297:Male; D008657:Metabolic Clearance Rate; D009543:Nifedipine / Q000097:blood / Q000493:pharmacokinetics*; D010936:Plant Extracts / Q000009:adverse effects / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D013440:Sulfides / Q000008:administration & dosage / Q000009:adverse effects*; D013997:Time Factors; D014665:Vasodilator Agents / Q000097:blood / Q000493:pharmacokinetics*
chemical_list: D000498:Allyl Compounds; D002121:Calcium Channel Blockers; D010936:Plant Extracts; D010975:Platelet Aggregation Inhibitors; D013440:Sulfides; D014665:Vasodilator Agents; C042577:diallyl trisulfide; D009543:Nifedipine