Pharmacokinetics of clindamycin HCl administered intravenously, intramuscularly and subcutaneously to dogs

ABSTRACT

A buffered aqueous solution of clindamycin Hcl (200 mg/mL) was injected intravenously (i.v.) intramuscularly (i.m.) and subcutaneously (s.c.) in a non-randomized, partial cross-over trial involving six male and six female dogs. Blood samples were collected at conventional, predetermined time periods and serum drug concentrations were determined by microbiological assay. Dogs were observed clinically for signs of pain, and activity of serum creatine phosphokinase (CPK) was monitored after i.m. dosing.

The i.v. data from five of the dogs best fitted a two-compartment open-system pharmacokinetic model whereas a non-compartment model was most suitable for analysis of the data from the remaining seven dogs. The mean i.v. elimination half-life (t_½β) and the mean residence time (MRT) were 124 and 143 min, respectively. The mean volume of distribution at steady state (V_ss) was 0.86 L/kg. Little pain was recorded upon i.m. injection; mean peak serum drug concentration (C_max) was 4.4 μg/mL, the elimination half-life (t_½el) was 247 min and the calculated bioavailability (F) was 115% of the i.v dose. Serum CPK activity was elevated to 25-fold the pretreatment level in samples collected 4, 8 and 12 h after i.m. injection. Pain was not recorded after s.c. drug administration; the mean C_max of 20.8 μg/mL was significantly greater than the corresponding value for the i.m. route, and F was 310%. The s.c. route appears to be superior to the i.m. route in terms of local tolerance and serum drug level; a 10 mg/kg SID treatment regimen is suggested for treatment of canine infections due to clindamycin sensitive bacteria.