Systemic bioavailability of nasally applied chlorphenamine maleate (0.4% nasal spray) relative to tablets administered perorally.
OBJECTIVE
This study investigated the bioavailability of single doses of 1.12 and 2.24 mg chlorphenamine maleate applied intranasally (0.4% nasal spray) relative to a single peroral dose of 8 mg chlorphenamine maleate (tablets).


METHODS
Twenty-four (24) subjects were treated with single nasal doses of 1.12 mg and 2.24 mg chlorphenamine maleate (0.4% nasal spray) and two 4 mg chlorphenamine maleate tablets (Piriton) on 3 separate study days according to a 3-way cross-over design with a 7-day wash-out between periods. Blood was sampled before and at 0.25, 0.50, 1.0, 2.0, 3.0, 4.0, 6.0, 8.0, 12, 16 and 24 hours after drug administration. Additional blood samples were obtained 36, 48 and 72 hours after peroral administration only. All subjects were included in the pharmacokinetic analysis.


RESULTS
Nasally applied chlorphenamine maleate was readily absorbed, reaching peak plasma levels after 0.25 to 3.0 hours. The dose-normalized estimated mean Cmax values were 1.24, 1.43 and 1.21 ng/ml for the peroral tablet and the 1.12 mg and 2.24 mg nasal dose, respectively. The dose-normalized estimated mean AUC(0-infinity) values were 25.91, 26.44 and 25.56 ng x h/ml for the tablet and the 1.12 and 2.24 mg nasal dose, respectively. The estimated treatment ratios (nasal dose to tablet) of the dose-normalized values for the 1.12 mg nasal dose were 1.15 (900 CI: 1.0-1.32) and 1.02 (90% CI: 0.88-1.18) for Cmax and AUC(0-infinity), respectively, for the 2.24 mg nasal dose they were 0.98 (90% CI: 0.85-1.13) and 0.99 (90% CI: 0.85-1.13) for Cmax and AUC(0-infinity), respectively. The other pharmacokinetic characteristics (tmax, t(1/2), lambda(z), AUC(0-tf), MRTtot, CL/f and Vz/f) were comparable across all treatments. These data indicate that the disposition of chlorphenamine maleate was independent of the route and dose of administration.


CONCLUSIONS
Chlorphenamine maleate is readily absorbed after nasal application using a 0.4% nasal spray. The nasal administration showed that the systemic bioavailability at the two dose levels used was comparable to that for the tablet. Maximum concentrations on the low dose, however, were higher and those on the high dose were comparable to those for the tablet. The nasal application of chlorphenamine maleate does not alter the overall systemic exposure compared to the oral route.
Van Toor
B S
BS
Research, Development and Medicine, Boehringer Ingelheim GmbH, Germany. bert.vantoor.bt@bayer-ag.de
Buchwald
A
A
Stengele
E
E
Trenk
D
D
Gercek
C
C
de Mey
C M
CM
D000281:Administration, Intranasal; D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002744:Chlorpheniramine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D006207:Half-Life; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D013607:Tablets
D006634:Histamine H1 Antagonists; D013607:Tablets; D002744:Chlorpheniramine