Abstract | PURPOSE: METHODS: The pharmacokinetic studies were carried out following administration of 40 mg/kg of racemic HCQ to diabetic, insulin-treated diabetic, adjuvant arthritic and control rats. RESULTS: Renal (70% and 62% for R- and S-HCQ, respectively) and non-renal clearance (100% and 145% for R- and S-HCQ, respectively) of HCQ enantiomers were significantly increased in diabetic rats. Diabetes-induced alterations in the disposition of HCQ were reversed by insulin treatment. In arthritic rats, systemic clearance (CL) of HCQ enantiomers was significantly reduced (1.05 +/- 0.15 and 1.3 +/- 0.19 l/h/kg for R- and S-HCQ, respectively) compared to controls (1.69 +/- 0.32 and 1.93 +/- 0.34 l/h/kg for R- and S-HCQ, respectively). The fraction unbound of the R- and S-HCQ were 49.4% and 50.5% lower in platelet rich plasma of arthritic rats compared to healthy rats. Increased blood concentrations of HCQ enantiomers in arthritic rats were significantly related to the degree of inflammation. CONCLUSIONS: Diabetes significantly increased the CL of both R- and S-HCQ by increasing renal and non-renal clearance. Arthritis caused a significant decrease in CL of HCQ enantiomers through increased binding and a decreased intrinsic clearance. The effect of the diseases on the pharmacokinetics of HCQ, however, was not stereoselective.
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Authors | J Emami, F M Pasutto, F Jamali |
Journal | Pharmaceutical research
(Pharm Res)
Vol. 15
Issue 6
Pg. 897-903
(Jun 1998)
ISSN: 0724-8741 [Print] United States |
PMID | 9647356
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antirheumatic Agents
- Hydroxychloroquine
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Topics |
- Animals
- Antirheumatic Agents
(chemistry, pharmacokinetics)
- Arthritis, Experimental
(metabolism)
- Diabetes Mellitus, Experimental
(metabolism)
- Hydroxychloroquine
(chemistry, pharmacokinetics)
- Male
- Rats
- Rats, Sprague-Dawley
- Stereoisomerism
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