The lack of effect of inoculation with equine influenza vaccine on theophylline pharmacokinetics in the horse

Abstract

Several studies conducted during the past few years have shown that the pharmacokinetics of a variety of drugs may be altered following viral infection or vaccination. The elimination of drugs which are extensively metabolized, such as theophylline, may be prolonged, especially following exposure to RNA viruses such as Type A influenza or similar orthomyxoviruses. The purpose of this study was to determine whether vaccination of horses with equine influenza virus affected pharmacokinetic parameters describing the distribution and elimination of intravenously administered theophylline. Three thoroughbred horses and three ponies were vaccinated with a trivalent vaccine containing inactivated strains of A/Equi 1 (Prague), A/Equi 2 (Miami) and A/Equi 2 (Kentucky 81). Antibody titre, serum interferon concentrations, and the pharmacokinetic parameters t1/2 beta, Vc, Vd(ss), Vd(area) and ClB were measured at various intervals after vaccination. Antibody titre increased substantially in only two animals, while plasma interferon was detectable in low concentrations in four subjects. There was no significant change in any parameter describing the pharmacokinetics of theophylline when measured 2, 6, or 12 days after vaccination. It is suggested that the failure of vaccination to substantially increase plasma interferon concentrations, and thereby alter theophylline elimination, was related to the use of an inactivated viral vaccine, the only type available for vaccination of horses against infection with equine influenza. Regular use of such vaccines, as is required by most Racing Authorities, is therefore unlikely to affect drug withdrawal times.

The pharmacokinetics of a slow-release theophylline preparation in horses after intravenous and oral administration

“…This value agrees with some previous reports (Errecalde et al, 1984;Ingvast Larson et al, 1985), although a faster elimination rate was reported by Short et al (1986).…”

“…However, values smaller than ours (mean 298 ml) were found by Short et al (1986). The mean apparent volume of distribution (Va) of 1.35 L/kg indicates extensive distribution to the extravascular tissues.…”

“…This result is larger than those given by Ingvast-Larson et al (1985) (1.02 L/kg) and by Ayres et al (1985) (1.02 L/kg). Even smaller volumes were reported by Errecalde et al (1984) (0.85 L/kg) and Short et al (1986) (0.703 L/kg), although in all these studies the V a values can be considered as relatively high.…”

“…There are previous reports concerning the pharmacokinetic behaviour of theophylline after intravenous and/or oral administration (Errecalde et al, 1984;Kowalczyk et al, 1984;Ayres et al, 1985;Ingvast Larson et aL, 1985;Short et al, 1986). However, there are no reports of the pharmacokinetics of the sustained release form of this drug in horses.…”

Vaccine–Drug Interactions: Cytokines, Cytochromes, and Molecular Mechanisms

“…The possibility of an interaction was therefore suspected and reported in cases in which signs and symptoms of carbamazepine toxicity were observed a few days after immunization [69]. Vaccination has also been reported to influence serum concentrations of other drugs including theophylline [70][71][72][73][74][75], chlordiazepoxide, phenytoin, phenobarbital, and lorazepam [16].…”