ArticlePharmaceutical research1998
Effect of experimental diabetes mellitus and arthritis on the pharmacokinetics of hydroxychloroquine enantiomers in rats.
Article in Pharmaceutical research, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 32 citations in OpenAlex.
- Influence of gestational diabetes on the stereoselective pharmacokinetics and placental distribution of metoprolol and its metabolites in parturients.British journal of clinical pharmacology · 2015Trial
- Pharmacokinetics of lidocaine and its metabolite in peridural anesthesia administered to pregnant women with gestational diabetes mellitus.European journal of clinical pharmacology · 2008Trial
- Decreased dromotropic response to verapamil despite pronounced increased drug concentration in rheumatoid arthritis.British journal of clinical pharmacology · 2000Trial
- The In Vitro, In Vivo, and PBPK Evaluation of a Novel Lung-Targeted Cardiac-Safe Hydroxychloroquine Inhalation Aerogel.AAPS PharmSciTech · 2023Article
- Physiologically Based Pharmacokinetics of Lysosomotropic Chloroquine in Rat and Human.The Journal of pharmacology and experimental therapeutics · 2021Article
- Effect of type 2 diabetes mellitus on the pharmacokinetics and transplacental transfer of nifedipine in hypertensive pregnant women.British journal of clinical pharmacology · 2017Article
- Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid arthritis and related diseases.Inflammopharmacology · 2015Review
- Drug-disease interaction: Crohn's disease elevates verapamil plasma concentrations but reduces response to the drug proportional to disease activity.British journal of clinical pharmacology · 2011Article
- Despite increased plasma concentration, inflammation reduces potency of calcium channel antagonists due to lower binding to the rat heart.British journal of pharmacology · 2003Article
- Effect of experimental diabetes mellitus and arthritis on the pharmacokinetics of hydroxychloroquine enantiomers in rats.Pharmaceutical research · 1998Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo study the effect of experimental diabetes and arthritis on the pharmacokinetics of hydroxychloroquine (HCQ) enantiomers in rats.
methodsThe pharmacokinetic studies were carried out following administration of 40 mg/kg of racemic HCQ to diabetic, insulin-treated diabetic, adjuvant arthritic and control rats.
resultsRenal (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.
conclusionsDiabetes 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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