The successful treatment of acute and chronic osteomyelitis with the antibiotic lincomycin (Upjohn) has been the subject of several recent reports (Holloway, Kahlbaugh & Scott, 1963;Geddes, Sleet & McMurdoch, 1964;McLeod, Ross, Ozere, Digout & Van Rooyen, 1964;Grondin, St. Martin & Potvin, 1965; Holloway & Scott, 1965;Kaplan, Chew & Weinstein, 1965;McMillan, McRae & McDougall, 1967). While the investigations of Myer & Lewis (1963) and Ma, Lim & Nodine (1963) have elucidated the general pharmacokinetics of lincomycin, knowledge about the concentration in bone is incomplete and more information would be of interest.In osteomyelitis patients treated with lincomycin, Holloway, Kahlbaugh & Scott (1963) found concentrations ranging from 1.1 to 6.6 ug/g of bone. Simultaneous determinations of serum concentrations showed these to be higher than those in bone. As calculated from the data of the authors, the amount found in bone was 13.3 to 18.3% of that in serum.Conflicting results were published by Grady & Stern (1965). In their study in rats, the bone concentration regularly exceeded the serum concentration after a single oral administration of 100 mg/kg of an aqueous lincomycin solution. However, no appreciable binding of lincomycin to bone (for example by chelate formation as with tetracycline) was noted.The experiments described below were carried out to investigate further the concentrations of lincomycin in serum and bone in rats.
METHODSNormal albino rats with an average weight of 150 g were used. Each was given a single dose of 20 mg/kg lincomycin HCL. To avoid the wide variation of serum concentration commonly observed after oral administration because of variability in absorption, the dose was injected intramuscularly in aqueous solution. Animals were killed at intervals after the dose and the lincomycin content of serum and bone assayed. In the second part of the study 10 rats were treated with repeated injections of 20 mg/kg 12-hourly for 6 days and on the morning of the seventh day. Antibiotic concentrations in bone and serum of 2 animals were determined 1, 1, 2, 4 and 6 hr after the last injection. For all experiments lincomycin hydrochloride was used, provided in vials containing 20 mg. (Upjohn, Lot 14,.The concentration of the antibiotic in serum and bone was determined by means of the agar diffusion technique (cup plate method). The agar was autoclaved and then adjusted to pH 7.8.