The kinetics and disposition of chloroquine (CQ) and its metabolite monodesethylchloroquine (CQM) were investigated in 5 healthy volunteers after incremental (150-300-600mg CQ base) single oral doses of CQ. The analytical method used (HPLC and fluorescence detection) is the most sensitive known method for CQ and CQM. Plasma and whole blood concentrations of CQ, CQM and a third metabolite, bidesethylchloroquine (CQMM), were determined. The kinetics of CQ was found to be unique. The best fit was obtained by a multicompartmental model. The biological half-life appeared to be between 30-60 days; the volume of distribution (Vd) was approximately 8001/kg, and the clearance approximately 11/h/kg when calculated from plasma data. The whole blood concentrations were approximately 8-10 times higher than in plasma, and consequently the Vd and whole blood clearance were approximately 10 times lower. The kinetics changed as the dose was increased. An indication of capacity-limited steps in CQ disposition was found, as the rate constants decreased even though the clearance remained the same. The intrinsic half-life of CQM was 1/4 of that of CQ, but was prolonged after the highest dose of CQ. The present knowledge of CQ kinetics could provide a basis for revision of current dosage regimens in malaria suppression and rheumatoid disease to ensure efficacious and safe therapy.

Serum concentrations of chloroquine were determined fluorometrically in 100 rheumatoid patients who had been treated with 0.25 gm daily for at least 2 mo. The total dose varied between 3.7 and 400 gm. No patient received more than 75 gm annually. In 15% of the patients side effects were noted. There was a relationship between serum concentrations and side effects but not with the total dose administered. Chloroquine displayed dose-dependent kinetics, which may indicate that close monitoring of serum concentrations is an aid to the safe and rational use of the drug.

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The steady state disposition of chloroquine and its major metabolites, monodesethyl and bidesethyl chloroquine, were determined in 6 patients on long-term treatment for rheumatic disease with 99-155 mg base/day. The total body clearance of chloroquine was 0.35 l/kg/h and that of its metabolites was much higher. The renal clearance was the same for all compounds measured, approximately equal to 0.1 l/kg/h. Currently recommended dosage schedules appear to be too high in certain cases.

Arthritis of the sacro-iliac joints is a fairly common condition occurring either in isolation or as a part or pelvospondylitis. Because of the difficulty of establishing a diagnosis before X-ray changes have appeared, various radionuclide scanning techniques have been developed to make possible an early diagnosis. Opinions have differed as to the reliability of radionuclide methods using "bone seeking" radiopharmaceuticals. Patients with clinically and/or radiologically proven sacro-iliitis were imaged by means of 99m-Tc-EHDP. An S.I. index was calculated as the ratio of the maximum activity of the sacro-iliac joints to the minimum activity of the iliac wings. The accuracy of the method was very good, and it is recommended as a supplement to clinical examination and X-ray studies.