ABSOLUTE BIOAVAILABILITY OF MOXONIDINE

In a randomized 2-way cross-over study with eighteen healthy male volunteers, two moxonidine preparations (tablets, treatment A vs. intravenous solution, treatment B) were tested to investigate absolute bioavailability and pharmacokinetics of moxonidine. The preparations were administered as single doses of 0.2 mg; prior to and up to 24 h after administration blood samples were collected and the plasma moxonidine concentrations determined. Urine samples were collected prior to and at scheduled intervals up to 24 h after administration for the determination of unchanged moxonidine. Moxonidine plasma and urine concentrations were determined by a validated gas chromatographic/mass spectrometric method with negative ion chemical ionization. The mean areas under the plasma concentration/time curves were calculated as [mean +/- standard deviation] 3438 +/- 962 pg.h/ml (AUC(0 --> T(last)) and 3674 +/- 1009 pg.h/ml (AUC(0 --> infinity)) for treatment A; 3855 +/- 1157 pg.h/ml (AUC(0 --> T(last)) and 4198 +/- 1205 pg.h/ml (AUC(0 --> infinity)) for treatment B. Mean peak plasma concentrations of 1495 +/- 646 pg/ml were attained at 0.56 +/- 0.28 h after oral treatment, mean peak plasma concentrations after intravenous treatment reached 3965 +/- 1342 pg/ml at 0.17 +/- 0.01 h (= coinciding with end of infusion). The mean terminal half-lives of moxonidine were derived as 1.98 h after administration of the tablet and as 2.18 h after infusion. The amounts of moxonidine excreted in urine during the 24 h following administration (Ae(24h)) in absolute figures and as percentage of the dose administered were 102 +/- 26-mu-g or 51 +/- 13% for the tablet and 122 +/- 33-mu-g or 61 +/- 16% for the infusion. The relative bioavailability of oral moxonidine (assuming the availability of the i.v. solution to be 100%) was calculated to be 89% or F = 0.89 (AUC(0 --> T(last))) and 88% or F = 0.88 (AUC(0 --> infinity)). Taking these results into account, the relative amount of moxonidine excreted in urine of the dose absorbed comes up to approximately 58% for the tablet, which is comparable to an excretion of 61% of the dose administered (= absorbed) after i.v. administration. With the self-evident exception of C(max), statistical testing of pharmacokinetic parameters revealed no significant differences between treatments.