In-vivo pharmacokinetic characteristics of a transdermal phenylpropanolamine (PPA) preparation.

Phenylpropanolamine hydrochloride (PPA-HCL) is a synthetic phenylisopropanolamine sympathomimetic agent which is structurally related to ephedrine and amphetamine. Although its precise mechanism of action has not been conclusively determined, PPA is known to exert cardiovascular effects possibly related to indirect stimulation of beta-adrenergetic receptors in the heart. In addition, through CNS stimulation, PPA is known to act as an appetite suppressant, the anorexigenic effect being much weaker than that of amphetamine. In order to develop a convenient dosage of PPA, a transdermal preparation containing 250 mg PPA has been developed. Transdermal delivery is convenient both in terms of case of application and ready withdrawal of drug if desired. Oral PPA dosage forms are designed to have a fall off period of 6-8 hours to facilitate sleep. Such a drug free period is easily attained using a transdermal system either by removal of the transdermal device or incorporation of a lag period into the design of the system. The bioavailability and in vitro pharmacokinetic characteristics of this novel PPA preparation were compared with those of a reference sustained-release 75 mg Q16 PPA tablet (Acutrim), in a pilot, 3 subject, unblinded, cross-over, single dose study. Subjects fasted from the evening before dosing until 0.5 hours prior to dosing. Patches were removed 24 hours following application. Reportedly effective plasma PPA levels for appetite suppression were recorded after patch application and were comparable to those observed with the reference. Peak plasma PPA levels were slightly higher for the transdermal patch compared with the tablet formulation (93.6 ng/ml versus 80.10 ng/ml respectively).(ABSTRACT TRUNCATED AT 250 WORDS)