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

Abstract

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 3×3 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 h 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 µg/ mL (single, 100 mg doxycycline), 4.20 ± 1.34 µg/mL (single, 200 mg doxycycline), 6.69 ± 1.26 µg/mL (single-dose, 300 mg doxycycline) and 3.05 ± 0.92 µg/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–∞) were 21.85 ± 6.37 µg · h/mL, 52.02 ± 15.26 µg · h/mL, 84.86 ± 23.03 µg · h/mL and 34.64 ± 5.89 µg · h/mL, AUC_0–48 were 19.75 ± 6.60 µg · h/mL, 46.13 ± 12.21 µg · h/mL, 75.57 ± 20.31 µg · h/mL and 32.03 ± 5.70 µg · h/mL, for single dose of 100, 200, 300 mg doxycycline 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.

Key words

Antibiotics - CAS 24390-14-5 - Doxycycline hydrochloride, intravenous infusion, multiple-dose, pharmacokinetics, single-dose - Tetracyclines

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