PHARMACOKINETICS OF APOMORPHINE IN PARKINSONS-DISEASE - PLASMA AND CEREBROSPINAL-FLUID LEVELS IN RELATION TO MOTOR-RESPONSES

In this study, we measured the relationship between plasma and cerebro spinal fluid (CSF) apomorphine levels and their clinical effects in tw o patients with Parkinson's disease (PD). After subcutaneous injection of apomorphine, serial samples of plasma and lumbal CSF were taken an d serial scoring of motor responses was done using the Webster Rating Scale. The ratio of the highest level of apomorphine in CSF and plasma was 0.036 for patient A and 0.025 for patient B. The time lag between the highest level of apomorphine in plasma and CSF was 20 min for pat ient A and 10 min for patient B. Plasma levels of apomorphine correlat ed weakly with clinical motor responses. However, we could establish a highly strong correlation between apomorphine CSF levels and clinical motor responses: 0.93 and 0.89 for patients A and B, respectively. We conclude that a two-compartment pharmacokinetic model explains the cl inical effects of apomorphine better than does a one-compartment model . In a two-compartment model, clinical effect can clearly be correlate d to apomorphine levels in the central compartment.