POPULATION PHARMACOKINETICS OF APOMORPHINE IN PATIENTS WITH PARKINSONS-DISEASE

The population pharmacokinetic parameters of apomorphine, a potent dop amine agonist used in the treatment of on-off fluctuations in 8 Parkin sonian patients, were calculated after subcutaneous and intranasal adm inistration. Compared with the 'traditional' standard 2-stage method o r naive pooling, the nonparametric expectation maximization method (NP EM2) program from the USCPACK collection provides similar results, bu t more information about the population under investigation. Two avail able software packages for therapeutic drug monitoring were used: USC PACK and MW/PHARM. We compared the calculated parameters: elimination constant (k(el)), distribution volume (V-slope), absorption constant ( k(a)) and bioavailability. Small differences were observed in the foll owing population pharmacokinetic data: Subcutaneous administration (n = 8): V-slope = 1.89 +/- 0.97 L/kg, k(el) = 1.46 +/- 0.63 hour(-1), k( a) = 10.5 +/- 7.6 hour(-1) Intranasal administration (n = 6): V-slope = 1.68 +/- 0.71 L/kg, k(el) = 1.41 +/- 0.58 hour(-1), k(a) = 9.45 +/- 4.97 hour(-1), bioavailability 1.32 +/- 0.81. It was concluded that th e nasal route is a good alternative to the subcutaneous route of admin istration.