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Enrofloxacin, a quinolone antibiotic developed exclusively for use in animals, was investigated for its effects on the steady-state pharmacokinetics of theophylline in six healthy Beagle dogs. A sustained-release theophylline formulation was given alone (20 mg/kg per os twice daily at 12 h intervals) for 9 days and then co-administered with enrofloxacin (5 mg/kg i.v. once a day) for 5 days. Mean trough theophylline concentrations progressively and significantly increased during the five days of enrofloxacin co-administration. Theophylline clearance and concentration-time profile were significantly changed by enrofloxacin co-administration. No significant change was observed in enrofloxacin pharmacokinetics. The kinetic interaction between theophylline and enrofloxacin could be of clinical significance and may require plasma drug concentration monitoring and adjustment of theophylline dosage.

The pharmacokinetics of cephalexin, a first generation cephalosporin, were investigated in dogs using two formulations marketed for humans, but also often employed by practitioners for pet therapy. Cephalexin was administered to five dogs intravenously and intramuscularly as a sodium salt and by the oral route as a monohydrate. The dosage was always 20 mg/kg of active ingredient. A microbiological assay with Sarcina lutea as the test organism was adopted to measure cephalexin concentrations in serum. The mean residence time (MRT) median values after intravenous (i.v.), intramuscular (i.m.) and oral administration (p.o.) were 86 min, 200 min, and 279 min, respectively. After i.m. and oral dosing the peak serum concentrations (24.2 +/- 1.8 micrograms/mL and 20.3 +/- 1.7 micrograms/mL, respectively) were attained at 90 min in all dogs and bioavailabilities were 63 +/- 10% and 57 +/- 5%, respectively. The time course of the cephalexin serum concentrations after oral administration was best described by a model incorporating saturable absorption kinetics of the Michaelis-Menten type: thus in the gastrointestinal tract of dogs a carrier mediated transport for cephalexin similar to that reported in humans, may exist. The predicted average serum concentrations of cephalexin after repeated i.m. and oral administration indicated that, in order to maintain the therapeutic concentrations, the 20 mg/kg b.w. dosage should be administered every 6-8 h.

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Praziquantel (PZQ) is a broadly effective trematocide and cestocide, widely employed in veterinary and human medicine. In view of several differences in both its pharmacokinetic profile in different animal species and in the cytochrome P450-dependent system between ruminant and nonruminant species, the present study was undertaken to determine the pharmacokinetics of this drug, its effects on the P450 system and the involvement of cytochrome P450 in its metabolism in 3-month-old lambs infested by Fasciola hepatica. Following both oral and i.m. administration, PZQ disposition was best described by a linear one-compartment open model with a rapid absorption and elimination. Although the PZQ dose used by the i.m. route was only half of that used by the oral route, the mean PZQ plasma concentration was higher after i.m. than after oral treatment. Oral treatment with 30 mg/kg/day of PZQ did not modify the mono-oxygenase activities tested, whilst the administration of PZQ at a dose of 60 mg/kg/day for 2 days caused a significant decrease in the P450 3A-dependent erythromycin N-demethylase and 6beta testosterone hydroxylase activities. From the incubation of microsomes from lambs not treated with PZQ, a single metabolite (PZQ 11b-OH or PZQ 1-OH) was identified by GC/MS analysis. By selective inhibition of the 3A subfamily performed with triacetyloleandromycin, the production of this metabolite declined by about 90% suggesting a prominent role of P450 3A isoforms in this oxidation. These features indicate that agents or drugs which are able to modulate P450 3A-dependent catalysis may interfere with the metabolism, bioavailability and therapeutic effects of PZQ.

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It is not known if diastolic abnormalities are independent of systolic dysfunction in arterial hypertension. We studied three groups of 10 male subjects of comparable mean age (31.6 +/- 3.5 years), weight, and height: Athletes (A) (cyclists), essential hypertensive patients (H), and controls (C). Ultrasonic myocardial integrated backscatter signals (IBS) of the septum and the posterior wall were analyzed, while the systo-diastolic variation of the backscatter was considered as a cyclic variation index (CVI(ibs)). Myocardial velocities across the left ventricular major axis were sampled at septum and lateral wall levels by pulsed-wave Doppler tissue imaging (DTI). CVI(ibs) at the septum and the posterior wall were significantly lower in the hypertensive group in comparison with athletes and controls, who were comparable. Early diastolic myocardial velocity (E(m)) of the lateral wall and of the septum were significantly lower in hypertensives, while the late diastolic myocardial velocity (A(m)) was significantly higher in hypertensives in comparison with athletes. The E(m)/A(m) at the septum level was significantly lower in hypertensives in comparison with athletes and controls. Significant correlations were found between CVI and DTI parameters: CVI(ibs) and E(m)/A(m) septum (r = 0.50, P < 0.002). Furthermore, significant correlations were found between mean arterial pressure (MAP) and E(m)/A(m) septum (r = - 0.65, P < 0.001). Ultrasonic tissue characterization with the intrinsic contractility study and the evaluation of the regional diastolic function should, therefore, represent a new integrated diagnostic modality for the evaluation of left ventricular hypertrophied intramyocardial function. This study demonstrated that diastolic abnormalities of left ventricular function, in arterial hypertension, are related and progress with systolic intrinsic dysfunction.