The influence of liposomal encapsulation on sodium cromoglycate pharmacokinetics in man.
The pharmacokinetics of pulmonary-administered sodium cromoglycate (SCG) has been studied in five healthy volunteers. SCG, 20 mg, was inhaled as a solution and encapsulated in dipalmitoyl phosphatidylcholine/cholesterol (1:1) liposomes. Liposomal SCG produced detectable drug levels in plasma from four volunteers taken 24 and 25 hr after inhalation. Inhaled SCG solution, although producing peak plasma levels more than sevenfold greater than liposomal drug, was not detectable in 24-hr samples from any volunteer. The decline in plasma levels following inhalation of liposomal SCG (reflecting the absorption phase) was best described by a biexponential equation. The two absorption rate constants differed by more than an order of magnitude. The rapid absorption phase was probably due to free or surface-adsorbed SCG in the liposomal formulation, since the absorption rate constant for this phase did not differ significantly from the absorption rate constant for SCG in solution. The phase of slow drug absorption may then be attributed to absorption of drug released from vesicles. The data indicate that encapsulation of SCG prior to pulmonary administration prolonged drug retention within the lungs and altered its pharmacokinetics.
Taylor
K M
KM
School of Pharmacy, University of London, England.
Taylor
G
G
Kellaway
I W
IW
Stevens
J
J
D015060:1,2-Dipalmitoylphosphatidylcholine; D000293:Adolescent; D000328:Adult; D002214:Capsules; D004205:Cromolyn Sodium / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008081:Liposomes; D008297:Male; D010316:Particle Size
D002214:Capsules; D008081:Liposomes; D015060:1,2-Dipalmitoylphosphatidylcholine; D004205:Cromolyn Sodium