Effect of caffeine on the plasma protein binding and the disposition of ceftriaxone

The effects of caffeine on the in‐vitro protein binding and the pharmacokinetics of ceftriaxone (a highly protein bound cephalosporin) were investigated. Caffeine failed to decrease in‐vitro protein binding of ceftriaxone. Rabbit plasma concentrations of ceftriaxone (30 mg kg⁻¹ i. v.) were elevated significantly (P <005 at 0.3, 0.6 and 1 h after injection) when caffeine 5 or 10 mg kg⁻¹ i.v. was co‐administered compared with ceftriaxone given alone. Caffeine increased the volume of distribution of the central compartment (V₁) for ceftriaxone significantly from 49 ± 38 ml kg⁻¹ (mean ± s.d., n = 6) to 97 ± 33 ml kg⁻¹ (caffeine 5 mg kg⁻¹, P <0.05), and 94 ± 8 ml kg⁻¹ (caffeine 10 mg kg⁻¹, P <0.05) and decreased the volume of distribution of the peripheral compartment (V₂) from 145 ± 106 ml kg⁻¹ (mean ± s.d., n = 6) to 31 ± 18 ml kg⁻¹ (caffeine 5 mg kg⁻¹, P <0.05) and 36 ± 31 ml kg⁻¹ (caffeine 10 mg kg⁻¹, P < 0.1). The rate of transfer of ceftriaxone to the peripheral compartment (k₁₂) was also decreased significantly (P <0.05) after caffeine. The elevated plasma concentration of ceftriaxone, increased V₁ value and the decreased V₂ and k₁₂ values are probably the result of caffeine altering the distribution of ceftriaxone to the central and the peripheral compartments. 1985 Royal Pharmaceutical Society of Great Britain