Penicillamine kinetics in normal subjects

Abstract

The kinetic characteristics of penicillamine, used to treat rheumatoid arthritis and Wilson''s diseases are reported in 4 fasting subjects after 4 oral doses each. On later test days, 2 of the subjects received an additional single dose 30 min after a large breakfast. One subject originally included in the study had to drop out due to gastrointestinal disturbances following each of 2 single doses of penicillamine. The fasting plasma levels of penicillamine observed in this study displayed an unusual double peak in the plasma levels after single doses. Individual subjects had consistent plasma level patterns for each of the 4 single doses but there was marked intersubject variability in patterns and kinetic parameters. The half-life of unchanged penicillamine ranged from 1.66-3.15 h and the apparent plasma clearance ranged from 530-2300 ml/min. The administration of penicillamine following a large breakfast caused a reduction in the area under the penicillamine plasma concentration-time curve corresponding to a decrease in the extent of absorption of unchanged penicillamine.