Pharmacokinetics of Doxycycline Hydrochloride Administered by Intravenous Infusion in Healthy Chinese Volunteers

The pharmacokinetics of doxycycline hydrochloride (CAS 24390-14-5) was investigated In 11 healthy Chinese volunteers after single- and multiple-dose Intravenous (i. v.) Infusion. This study was conducted according to an open, randomized, four-period design with a one-week washout period separating each trial period. Single-dose studies with 100, 200, and 300 mg doxycycline were performed in the first three periods by a replicated 3 x 3 Latin square crossover design. Multiple-dose studies with once-daily 100 mg doxycycline for 7 consecutive days were performed in the last treatment period. Blood samples for pharmacokinetic profiling were taken up to 48 It post-infusion. Doxycycline hydrochloride plasma concentrations were determined with a validated liquid chromatography-ultraviolet (HPLC-UV) method. The pharmacokinetic parameters for single- and multiple-dose administration were estimated as follows: Maximum plasma concentrations (C-max) amounted to 1.49 +/- 0.59 mu g/mL (single, 100 mg doxycycline), 4.20 +/- 1.34 mu g/mL (single, 200 mg doxycycline), 6.69 +/- 1.26 mu g/mL (single-dose, 300 mg doxycycline) and 3.05 +/- 0.92 mu g/mL (multiple-dose, 100 mg doxycycline). The median T-max (2 h of infusion Included) was 2.00 +/- 0.19 h, 1.93 +/- 0.23 h, and 1.98 +/- 0.18 h for single dose of 100 mg, 200 mg, 300 mg doxycycline and 2.11 +/- 0.17 h for multiple dose of 100 mg doxycycline, respectively. Plasma elimination half-lives (t(1/2)) were 14.00 +/- 5.88 h, 14.20 +/- 8.11 h, 16.66 +/- 7.12 h and 14.03 +/- 3.50 h, areas under the plasma concentration-time curve (AUC(0-infinity)) were 21.85 +/- 6.37 mu g.h/mL, 52.02 +/- 15.26 mu g.h/mL, 84.86 +/- 23.03 mu g.h/mL and 34.64 +/- 5.89 mu g.h/mL, AUC(0-48) were 19.75 +/- 6.60 mu g.h/mL, 46.13 +/- 12.21 mu g.h/mL, 75.57 +/- 20.31 mu g.h/mL and 32.03 +/- 5.70 mu g.h/mL, for single dose of 100, 200, 300 mg doxycyctine and multiple dose of 100 mg doxycycline, respectively. AUC In the single-dose study were dose proportional, doxycycline hydrochloride showed first order kinetics in the range of 100-300 mg. The plasma concentration of doxycycline hydrochloride has been sustained at a certain effective level after multiple-dose treatment, and the elimination process was similar to that after the single dose. Gender differences were also observed.