Pharmacokinetics (PK) of intraveneous scopolamine (SCP) plus physostigmine (PHY) in healthy elderly male and female volunteers

Abstract

Purpose (1) To investigate the PK of SCP in healthy elderly volunteers, (2) To determine any PK interactions of PHY on SCP. Methods: Sixteen healthy elderly volunteers received 6.7μg/kg IV SCP/placebo, followed 60 minutes later by 6.7μg/kg IV PHY/placebo. Plasma SCP concentrations were measured by radio-receptor assay (LOQ: 100 pg/ml). Noncompartmental PK analysis was performed. ANOVA was used to assess gender, treatment and age differences. Results: CLtot was 2.9±1.5 l/min (mean±SD), while Vdss was 249±106 l, resulting in a terminal half-life (t1/2) of 72±19 min. No significant PK differences were found after co-administration of PHY. A gender difference was found for Vdss and t1/2, where males had a 45% higher Vdss and a 26% longer t1/2 than females. Significant age differences were found for CLtot and Vdss; the elderly showed higher values than those in the young. The following table shows PK parameters in the young (6M, 6F) and elderly healthy (8M, 8F) volunteers. (See Table) Conclusions SCP showed rapid, extensive distribution and high clearance values suggesting extrahepatic metabolism. PHY did not have any influence on SCP PK. Gender differences were found in Vdss and t1/2, and age differences were found in CLtot and Vdss, which may due to changes in plasma/tissue protein binding and/or extrahepatic metabolism. Clinical Pharmacology & Therapeutics (2004) 75, P34–P34; doi: 10.1016/j.clpt.2003.11.130 Table 1. Elderly Males Elderly Females Young Males Young Females CLtot (l/min) 3.5 (1.9) 2.3 (0.5) 1.7 (0.2) 1.4 (0.5) Vdss (l) 296 (128) 203 (55) 168 (52) 155 (60)