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.

Effects of HMG-CoA reductase inhibitors on the pharmacokinetics of nifedipine in rats: Possible role of P-gp and CYP3A4 inhibition by HMG-CoA reductase inhibitors

“…Our results were similar to those reported by Choi et al [29] and Hong et al [31] which showed that atorvastatin and lovastatin significantly increased the AUC 0-1 and C max of verapamil, a substrate of both CYP enzymes and P-gp in rats, and by Choi et al [43] which showed that simvastatin significantly increased the AUC and C max of diltiazem in rats. The results of these studies were also consistent with the report that oral diallyl trisulfide (major organosulfur compounds derived from garlic) significantly increased the bioavailability of nifedipine through inhibition of CYP3A4 in rats [46]. Our results are also consistent with those reported by Kuroha et al and Nishimura et al which showed that ketoconazole and Coenzyme Q 10 significantly increased the AUC 0-1 and C max of nifedipine [47,48].…”

Thiol, Disulfide, and Trisulfide Complexes of Ru Porphyrins: Potential Models for Iron–Sulfur Bonds in Heme Proteins

“…The natural products calichemicin and esperamicin, for instance, inaugurate a new class of potent antitumor antibiotics, , with mechanisms depending upon a complex chain of reactions triggered by a trisulfide moiety that cleaves DNA. , The cytotoxicity of varacin, a cyclic pentasulfide natural product, has been ascribed to radical, oxidative DNA damage (via Fenton-like chemistry), and derivatization to a trisulfide species possibly plays a key role in the biological activity . Studies on such activity of garlic and onion organosulfur compounds are also relevant here, in that their extracts are rich in diallyl trisulfide that has anticarcinogenic and antiproliferative activity in which modulation of cytochrome P450 activity has been implicated. , However, details of the trisulfide–hemoprotein interactions remain unknown.…”

Natural Products in Cardiovascular Diseases: The Potential of Plants from the Allioideae Subfamily (Ex-Alliaceae Family) and Their Sulphur-Containing Compounds

“…The effect of sulphur-containing compounds on the pharmacodynamic and pharmacokinetics of other drugs was also assessed. Indeed, it was reported that the oral co-consumption of diallyl trisulphide and nifedipine led to a higher maximum concentration and area under the curve, thus suggesting that the compound might affect the gastrointestinal metabolism of nifedipine, since no effect on the pharmacokinetics was observed when nifedipine was given intravenously [ 160 ].…”