A dose‐effect study of the in vivo inhibitory effect of quinidine on sparteine oxidation in man.

MD Nielsen*, K. Brosen, LF Gram

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1. Twelve healthy extensive metabolisers of sparteine were sparteine tested daily for 6 days (19.00 h to 07.00 h). A small but statistically significant rise in sparteine metabolic ratio (MR) was observed. 2. Following 100 mg quinidine sulphate given to four of the subjects at 16.00 h, sparteine tests were carried out 19.00 h to 07.00 h on the same day and then daily for 6 days. Quinidine caused an immediate twenty‐fold increase in sparteine‐MR which then gradually returned to normal over the following 4‐6 days. Quinidine concentrations in plasma were measurable only up to 20 h after the quinidine test dose. 3. At weekly intervals, all 12 subjects received single doses of quinidine sulphate of 5, 10, 20, 40 and 80 mg at 16.00 h, each time followed by a sparteine test 19.00 h to 07.00 h on the same day. A clear dose‐effect relationship was found with a significant rise in the sparteine‐MR even after 5 mg quinidine. After 80 mg quinidine, 8 of 12 subjects became phenotypically poor metabolisers (MR greater than 20). 1990 The British Pharmacological Society

TidsskriftBritish Journal of Clinical Pharmacology
Udgave nummer3
Sider (fra-til)299-304
Antal sider6
StatusUdgivet - 1. jan. 1990