Pharmacokinetics of erythromycin after the administration of intravenous and various oral dosage forms to dogs
G. A. ALBARELLOS V. E. KREIL L. A. AMBROS S. WAXMAN L. MONTOYA L. TARRAGONA P. C. QUAINE R. E. HALLU & M. REBUELTO
´ ´ Catedra de Farmacologıa, Facultad de Ciencias Veterinarias, Universidad de BuenosAires, Buenos Aires, Argentina
Albarellos, G. A., Kreil, V. E., Ambros, L. A., Waxman, S., Montoya, L., Tarragona, L., Quaine, P. C., Hallu, R. E., Rebuelto, M. Pharmacokinetics of erythromycin after the administration of intravenous and various oral dosage forms to dogs. J. vet. Pharmacol. Therap. 31, 496–500. The purpose of this study was to describe and compare the pharmacokinetic properties ofdifferent formulations of erythromycin in dogs. Erythromycin was administered as lactobionate (10 mg ⁄ kg, IV), estolate tablets (25 mg ⁄ kg p.o.) and ethylsuccinate tablets or suspension (20 mg ⁄ kg p.o.). After intravenous (i.v.) administration, the principal pharmacokinetic parameters were (mean ± SD): AUC(0–¥) 4.20 ± 1.66 lgÆh ⁄ mL; Cmax 6.64 ± 1.38 lg ⁄ mL; Vz 4.80 ± 0.91 L ⁄ kg; Clt 2.64 ±0.84 L ⁄ hÆkg; t½k 1.35 ± 0.40 h and MRT 1.50 ± 0.47 h. After the administration of estolate tablets and ethylsuccinate suspension, the principal pharmacokinetic parameters were (mean ± SD): Cmax, 0.30 ± 0.17 and 0.17 ± 0.09 lg ⁄ mL; tmax, 1.75 ± 0.76 and 0.69 ± 0.30 h; t½k, 2.92 ± 0.79 and 1.53 ± 1.28 h and MRT, 5.10 ± 1.12 and 2.56 ± 1.77 h, respectively. The administration of erythromycinethylsuccinate tablets did not produce measurable serum concentrations. Only the i.v. administration rendered serum concentrations above MIC90 = 0.5 lg ⁄ mL for 2 h. However, these results should be cautiously interpreted as tissue erythromycin concentrations have not been measured in this study and, it is recognized that they can reach much higher concentrations than in blood, correlating better withclinical efﬁcacy. (Paper received 11 December 2007; accepted for publication 9 May 2008) ´ Gabriela A. Albarellos, Chorroarın 280 (1427), Buenos Aires, Argentina. E-mail: email@example.com
INTRODUCTION Erythromycin is a macrolide antibiotic with many desirable properties which support its clinical use for the treatment of skin and other soft tissue infections in dogs (Hill & Moriello, 1994;Rosser, 2006). Its spectrum of activity includes many grampositive cocci (Staphylococcus intermedius, S. aureus, streptococci), Campylobacter spp., Pasteurella spp., Mycoplasma spp., some strains of Bordetella bronchiseptica and many anaerobic organisms (Noli & Boothe, 1999; Papich & Riviere, 2001). Erythromycin minimum inhibitory concentrations (MIC) are in the range of 0.015–1.0 lg ⁄ mL, thoughsome staphylococci strains could be much less sensitive (Lavy et al., 1995; Shimizu et al., 2001; Ganiere et al., 2005). The antibacterial activity of erythromycin depends on the maintenance of concentration above the MIC of susceptible micro-organism on which the drugs produces a time-dependent bacteriostatic effect. At concentrations well above (much higher than) the MIC, which may be attainedin some tissues, erythromycin could produce a bacte496
ricidal effect. Antibacterial activity is enhanced in an alkaline environment. The T>MIC is considered the most accurate pK ⁄ pD index of efﬁcacy (Toutain et al., 2002; McKellar et al., 2004). Erythromycin is widely used and has been extensively studied ´ ´ in human medicine (Patamasucon et al., 1981; Berube et al., 1988; Croteau et al.,1988) and in some domestic animal species (Soback et al., 1987; Burrows et al., 1989; Eriksson et al., 1990; Ewing et al., 1994; Bohlen et al., 1995; Lavy et al., 1995; Lakritz et al., 1999, 2000; Ambros et al., 2007). Erythromycin is highly lipid-soluble and is widely distributed throughout the body. It is a weak base with a pKa of 8.8 and is inactivated in the acidic environment of the stomach....