Steady-state pharmacokinetics of hydroxychloroquine in rheumatoid arthritis patients.

Steady-state pharmacokinetics of hydroxychloroquine (HC) sulfate (Plaquenil) were studied in five volunteers with rheumatoid arthritis who had taken 6 mg/kg/d of the drug for at least six months. Blood samples were drawn at 0, 1, 2, 4, 6, 8, 12, and 24 hours following an oral dose. Both whole blood and plasma were assayed by an HPLC method for HC and its metabolites desethylhydroxychloroquine, desethylchloroquine, and didesethylchloroquine. A 24-hour urine collection was obtained and assayed for the same compounds. The pharmacokinetics of HC and its metabolites conformed to the model predicted by single-dose studies. During the 24-hour period the absorption phase and both early and late distribution phases were seen. Variation in mean maximum/minimum concentration was 40 percent. Renal clearance accounted for only 16 percent of unchanged HC (22 percent of total drug and metabolites) and did not correlate with creatinine clearance.