Volume 23, Issue 7 p. 866-870

Coadministration of Milk Thistle and Indinavir in Healthy Subjects

Dr. Robert DiCenzo Pharm.D.

Corresponding Author

Dr. Robert DiCenzo Pharm.D.

University of Buffalo School of Pharmacy and Pharmaceutical Sciences, Buffalo, New York.

Department of Medicine, Infectious Disease Unit, University of Rochester Medical Center, Rochester, New York.

University of Rochester Medical Center, Department of Medicine, Room 3-6209, Box 689, 601 Elmwood Avenue, Rochester, NY 14642.Search for more papers by this author
Dr. Mark Shelton Pharm.D.

Dr. Mark Shelton Pharm.D.

University of Buffalo School of Pharmacy and Pharmaceutical Sciences, Buffalo, New York.

Search for more papers by this author
Dr. Kelly Jordan Pharm.D.

Dr. Kelly Jordan Pharm.D.

University of Buffalo School of Pharmacy and Pharmaceutical Sciences, Buffalo, New York.

Search for more papers by this author
Dr. Christine Koval M.D.

Dr. Christine Koval M.D.

Department of Medicine, Infectious Disease Unit, University of Rochester Medical Center, Rochester, New York.

Search for more papers by this author
Dr. Alan Forrest Pharm.D.

Dr. Alan Forrest Pharm.D.

University of Buffalo School of Pharmacy and Pharmaceutical Sciences, Buffalo, New York.

Search for more papers by this author
Dr. Richard Reichman M.D.

Dr. Richard Reichman M.D.

Department of Medicine, Infectious Disease Unit, University of Rochester Medical Center, Rochester, New York.

Search for more papers by this author
Dr. Gene Morse Pharm.D.

Dr. Gene Morse Pharm.D.

University of Buffalo School of Pharmacy and Pharmaceutical Sciences, Buffalo, New York.

Search for more papers by this author
First published: 16 January 2012
Citations: 78

Abstract

Study Objective. To determine if milk thistle (silymarin) alters the pharmacokinetics of indinavir.

Design. Sequential crossover trial.

Setting. General clinical research center.

Subjects. Ten healthy subjects.

Intervention. Indinavir 800 mg 3 times/day was given for four doses on days 1 and 2. Silymarin 160 mg 3 times/day was given on days 3–15. On day 16 and for one dose on day 17, both drugs were given at the same dosages.

Measurements and Main Results. Indinavir's pharmacokinetic parameters were evaluated at steady state both before and after administration of 14 days of silymarin. Blood samples were collected −0.25, 0.5, 1, 2, 3, 4, and 5 hours after indinavir dosing and assayed by high-performance liquid chromatography. The final pharmacokinetic model had first-order absorption after a lag time, and two compartments with first-order elimination from the central compartment. When given alone and combined with silymarin, respectively, the geometric mean (95% confidence interval [CI]) steady-state indinavir area under the plasma concentration-time curve was 20.7 hr·mg/L (15.3–28.2 hr·mg/L) and 19.4 hr·mg/L (15.8–23.6 hr·mg/L) and the trough plasma concentration was 0.340 mg/L (0.232–0.497 mg/L) and 0.232 mg/L (0.129–0.419 mg/L).

Conclusion. Silymarin has no apparent effect on indinavir plasma concentrations.