Systemic bioavailability of nasally applied chlorphenamine maleate (0.4% nasal spray) relative to tablets administered perorally

Aim: This study investigated the bioavailability of single doses of 1.12 an d 2.24 mg chlorphenamine maleate applied intranasally (0.4% nasal spray) re lative to a single peroral dose of 8 mg chlorphenamine maleate (tablets). M ethods: 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 ing 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 obtai ned 36, 48 and 72 hours after peroral administration only. All subjects wer e included in the pharmacokinetic analysis. Results: Nasally applied chlorp henamine maleate was readily absorbed, reaching peak plasma levels after 0. 25 to 3.0 hours. The dose-normalized estimated mean C-max values were 1.24, 1.43 and 1.21 ng/ml for the peroral tablet and the 1.12 ing and 2.24 mg na sal 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 an d 2.24 mg nasal dose, respectively. The estimated treatment ratios (nasal d ose to tablet) of the dose-normalized values for the 1.12 ing nasal dose we re 1.15 (90% CI: 1.0 - 1.32) and 1.02 (90% CI: 0.88 - 1.18) for C-max and A UC(0-infinity), respectively, for the 2.24 mg nasal dose they were 0.98 (90 % CI: 0.85 - 1.13) and 0.99 (90% Cl: 0.85 - 1.13) for C-max and AUC(0-infin ity) respectively. The other pharmacokinetic characteristics (t(max), t(1/2 ), lambda (z), AUC((0-tf)), MRTtot, CL/f and V-z/f) were comparable across all treatments. These data indicate that the disposition of chlorphenamine maleate was independent of the route and dose of administration. Conclusion s; Chlorphenamine maleate is readily absorbed after nasal application using a 0.4% nasal spray. The nasal administration showed that the systemic bioa vailability at the two dose levels used was comparable to that for the tabl et. Maximum concentrations on the low dose, however, were higher and those on the high dose were comparable to those for the tablet. The nasal applica tion of chlorphenamine maleate does not alter the overall systemic exposure compared to the oral route.