The effects of 1% lidocaine as a diluent on the pharmacokinetics and tolerance of ceftriaxone administered intramuscularly were investigated in 12 adult volunteers. Each subject received two 0.5-g doses of ceftriaxone (one in water and the other in 1% lidocaine) at least 1 week apart in a randomized crossover fashion. Plasma and urine samples were collected serially and assayed for ceftriaxone content by high-performance liquid chromatography. The mean peak plasma concentration, time to attain the peak, area under the plasma curve from time zero to infinity, and elimination half-life were 45 ,ug/ml, 2.5 h, 578 ,ug h/ml, and 7.1 h, respectively, after intramuscular administration of ceftriaxone in water diluent. The corresponding mean values in 1% lidocaine diluent were 42 ,g/ml, 3 h, 577 ,ug h/ml, and 7.0 h. The pharmacokinetic data suggested that 1% lidocaine does not alter either the elimination parameters or the bioavailability of intramuscularly administered ceftriaxone. The intensity and frequency of pain at the injection site were reduced considerably by the coadministered lidocaine.Ceftriaxone (Ro 13-9904), an experimental parenteral cephalosporin, displays a high order of activity against gram-positive and gram-negative bacteria and enhanced stability against various types of P-lactamases (6). The pharmacokinetic characteristics of ceftriaxone have been defined in normal healthy subjects after administration of single and multiple intravenous (i.v.) doses (5,6,9,11,12). The elimination half-life of ceftriaxone ranged from 5.9 to 8.8 h, considerably longer than the half-life range (0.6 to 3.0 h) reported for other experimental and marketed cephalosporins (6). Intramuscular (i.m.) administration of cephalosporins such as cefoxitin and cefamandole causes pain at the injection site. This can be reduced greatly by administering these cephalosporins in combination with a local anesthetic (2). In a preliminary study with six healthy volunteers, a single i.m. dose of 0.5 g of ceftriaxone dissolved in water produced moderate to severe pain (unpublished data). This observation led to the present study, in which two solutions of ceftriaxone (one in water and the other in 1% lidocaine diluent) were administered i.m. to 12 normal, healthy subjects in a randomized, crossover design. The influences of these diluents on the pharmacokinetics and pain parameters of ceftriaxone were compared.
MATERIALS AND METHODSSubjects. Twelve healthy adult subjects, 6 males and 6 females, ranging in age from 28 to 47 years (mean, 38 years) and in body weight from 51.6 to 86.8 kg (mean, 66.7 kg) participated in this study. All subjects gave written informed consent. Prestudy physical examination, a recent X ray, electrocardiogram, blood cell count, fasting blood sugar, blood urea nitrogen, bilirubin, creatinine, creatine phosphokinase (CPK), serum glutamic oxalacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, drug abuse screen, and urinalysis were normal for each subject. In first-time volunteers, a gluco...