Saquinavir Garlic

Formula, Natrol) used in the garlic-saquinavir study described above (41). In the study by Gurley et al. (39) garlic oil 500 mg did not result in appreciable differences in the 1-hydroxymidazolam/midazolam phenotypic ratio for CYP3A4, the enzyme that mediates the metabolism of saquinavir. Both studies administered the garlic preparations for at least three weeks, and therefore it is unlikely that the duration of therapy would account for the difference between studies. On the other hand, if allicin content is a critical issue, it may be that one of the reasons for the conflicting results between the two studies is potential variability in this active constituent in the two garlic preparations used. 

Saquinavir In a clinical study, the area under the curve for saquinavir decreased by 51% in patients taking garlic for 20 days it returned to 65% of baseline after a 10-day washout period. 

Piscitelli SC, Burstein AH, Welden N, Gallicano KD, Falloon J. The effect of garlic supplements on the pharmacokinetics of saquinavir. Clin Infect Dis 2002 34 234-238. 

Borek C. Garlic supplements and saquinavir. Clin Infect Dis 2002 35 343. Gilroy CM, Steiner JF, Byers T, Shapiro H, Georgian W. Echinacea and truth in labeling. Arch Intern Med 2003 163 699-704. 

Compared to baseline saquinavir pharmacokinetic parameters obtained in period 1, the use of garlic reduced the mean saquinavir area under the concentration-time curve (AUC) by 51%, and the maximum (Cmax) and minimum (Cmin) saquinavir concentrations by 54% and 49%, respectively. After a 10-day washout, the AUC, Cmax, and Cmin values were within a range of 60% to 70% of baseline values. The magnitude of the decline in concentration might result in therapeutic failure and viral rebound in patients with HIV. Based on the pharmacokinetic parameters obtained in period 3, it also appears that garlic might have a prolonged, albeit lesser, effect on saquinavir exposure. The effects of combined treatment with other protease inhibitors that are also potent cytochrome P-450 (CYP) enzymes modulators need to be further evaluated. 

Saquinavir PI2 Tablets and hard gel capsules 600 mg tid Take within 2 h of a full meal. Refrigeration recommended Nausea, diarrhea, rhinitis, abdominal pain, dyspepsia, rash See footnote 4 for contraindicated medications. Avoid in severe hepatic insufficiency. Use sunscreen owing to an increase in photosensitivity. Avoid concomitant garlic capsules... 

Because of reported antiplatelet effects, patients using anticlotting medications (eg, warfarin, aspirin, ibuprofen) should use garlic cautiously. Additional monitoring of blood pressure and signs and symptoms of bleeding is warranted. Garlic may reduce the bioavailability of saquinavir, an antiviral protease inhibitor, but it does not appear to affect the bioavailability of ritonavir. 

A garlic supplement reduced the plasma levels of saquinavir by 50% in one study, but had little effect in another. Another garlic supplement did not significantly affect the pharmacokinetics of a single dose of ritonavir. 

The mechanism of this interaction is uncertain, but it is thought that garlic reduced the bioavailability of saquinavir by increasing its metabolism in the intestine. Why there was a disparity in the effect of garlic on saquinavir between patients is unclear. 

Although information is limited, a reduction in saquinavir plasma levels of the magnitude seen in the first study could diminish its antiviral efficacy. All garlic supplements should probably be avoided in those taking saquinavir as the sole protease inhibitor (no longer generally recommended). While the pharmacokinetic effect on single-dose ritonavir was not clinically important, this requires confirmation in a multiple-dose study. 

Jacek H, Rentsch KM, Steinert HC, Pauli-Magnus C, Meier PJ, Fattinger K. No effect of garlic extract on saquinavir kinetics and hepatic CYP3A4 function measured by die erythromycin breath test Clin Pharmacol Ther (2004) 75, P80. 

Doses equivalent to two or more grams daily of fresh garlic may reduce plasma levels of saquinavir (Piscitelli et al. 2002). Also see Pharmacological Considerations for this entry. 

---