Evening dosing is associated with higher plasma concentrations of pranlukast, a leukotriene receptor antagonist, in healthy male volunteers.
OBJECTIVE
To study the magnitude of differences in the pharmacokinetics of pranlukast, after morning and evening administration.


METHODS
Pranlukast (300 mg) was administered to 12 healthy male volunteers on two separate occasions, either in the morning or evening. Both doses were given 30 min after a standard high fat content meal. Blood samples were collected up to 18 h postdose. Plasma was assayed by high performance liquid chromatography. Standard pharmacokinetic and statistical analyses were performed.


RESULTS
Statistically significant (P < 0.05) increases were noted in AUC(o,t) (56%) and tmax (2.5 h) after evening administration. Cmax was 14% higher after evening dosing (95% C.I. 0.71-1.84).


CONCLUSIONS
Pranlukast bioavailability is apparently increased after evening dosing as compared with morning administration. Higher night-time and early morning plasma concentrations may confer additional therapeutic benefit at a time when asthmatics are at greatest risk of developing bronchospasm.
Brocks
D R
DR
Smith Kline Beecham Pharmaceuticals, Department of Drug Metabolism and Pharmacokinetics, King of Prussia, PA 19406, USA.
Upward
J
J
Davy
M
M
Howland
K
K
Compton
C
C
McHugh
C
C
Dennis
M J
MJ
D000328:Adult; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002867:Chromones / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019454:Chronotherapy; D006207:Half-Life; D006801:Humans; D020024:Leukotriene Antagonists; D008297:Male; D008657:Metabolic Clearance Rate
D018927:Anti-Asthmatic Agents; D002867:Chromones; D020024:Leukotriene Antagonists; C047681:pranlukast