Bioavailability of penicillin V after oral administration to fed and fasted pigs

Abstract

Although penicillin G is one of the oldest antibiotics, it is stii very useful for the treatment of a number of infectious diseases in domestic animals caused by penicillin G sensitive pathogens. Of particular interest in veterinary practice are infections in pigs caused by Pasteurella multocida. Pasteurella haemolytica and Streptococcus suis. Penicillin G has, however, an important drawback in its rapid degradation under acidic conditions such as those found in the stomach of pigs. The resulting poor oral bioavailabdity makes penicillin G unsuited for administration as medicated feed, and thereby for herd treatment. Phenoxymethyl penicillin (penicillin V), on the other hand, is an acid resistant derivative of penicillin G with an almost identical antimicrobial spectrum (Soback et al., 1987), and intended for oral administration.Oral bioavailability of acid stable penicillins may, however, be quite low and furthermore be influenced by interactions with feed components (Mandell & Sande, 1990). The oral bioavailability of penicillin V was found to be around 30% in pre-ruminant calves (Soback et d., 1987), and variable in dogs depending on the feeding regime (Watson et al., 1987). In horses the bioavailability of penicillin V has been reported to be relatively low, thus requiring higher doses to achieve therapeutically active concentrations (Ducharme et al., 1983). However, penicillin V is inexpensive which means that, from an economic point of view at least, it is feasible to use larger doses to overcome the problem of low bioavailability.The aim of the present study was to determine the effect of feed on the bioavailability of penicillin V after oral administration to pigs, and the possibility of attaining therapeutically active concentrations by using a relatively high dose.Six clinically healthy cross-bred pigs 12 to 1 5-weeks-old and weighing 23-31 kg at the start of the first experiment, and 28-38 kg at the start of the third experiment, were used for the study. The pigs were kept individually with free access to water and fed a commercial feed mixture. The experiments were carried out in a 3-way crossover design with an interval of 1 week between each administration. Penicillin V (phenoxymethyl-penicillin-potassium) was dissolved in water (1 11 mg/ml correspond-ing to 100 mg/ml o ;he acid form of penicillin V) and administered intravenously (i.v.) to fed pigs through a catheter in a vein on the right ear at a dose of 0.1 ml/kg b.wt. corresponding to 10 mg penicillin V per kg b.wt. Blood samples were collected in heparinized tubes by means of a catheter in a vein on the left ear before and 2, 5, 10,15,20, 30,45,60 and 90 inin and 2, 3 , 4 , 6 , 8. 12, 15, 24, 30 and 48 h after administration of the drug. The oral dose (0.5 d / k g corresponding to 50 mg of penicillin V per kg b.wt.) was administered to fed and non-fed pigs through a stomach tube with a thin inner tube which was subsequently flushed with 20 ml water. Blood samples were obtained through a catheter placed in the left ear. Non-fed pigs were fasted...

Bioavailability of spiramycin and lincomycin after oral administration to fed and fasted pigs

“…(1992) where T max was estimated to be 3.7 h after administration of the drug mixed with feed. The absorption of both sulfadiazine and trimethoprim in pigs was slightly slower (Nielsen & Gyrd‐Hansen, 1994a) than for spiramycin, whereas penicillin V was absorbed at a faster rate (Nielsen & Gyrd‐Hansen, 1994b). Although MAT and MRT for spiramycin were longer in fed than in fasted pigs the difference was not significant due to a high variation in the group of fed pigs.…”

“…Besides, not all drugs are water soluble to such a degree that it is possible to obtain a therapeutically effective concentration after administration of the drug in drinking water. Administration of antibiotics mixed with feed may, however, in some cases result in interactions with feed components leading to reduced bioavailability dependent on the antibiotic in question as well as the animal species (Palmer et al ., 1983; Kniffen et al ., 1989; Yu et al ., 1990; Baggot, 1992; Sutter et al ., 1993; Nielsen & Gyrd‐Hansen, 1994a & b, 1996).…”

Interspecies Mixed-Effect Pharmacokinetic Modeling of Penicillin G in Cattle and Swine

“…Ranheim et al reported that the clearance of penicillin was lower in 1-week-old piglets than in adult pigs (7,51). Musser et al found that the volume of distribution at steady state (V ss ) of the calf was significantly higher than that of adult cattle (5,30).…”

Bioavailability of Enrofloxacin after Oral Administration to Fed and Fasted Pigs

“…Thus the bioavailability was not significantly influenced by the presence of feed in the gastrointestinal tract. For penicillin V the oral bioavailability was only 19% in fasted and 17% in (Nielsen & Gyrd-Hansen 1994b). In spite of the low bioavailability it was possible to obtain therapeutically active concentrations up to 6 hr after administration of 50 mg/kg body weight to fasted as well as fed pigs.…”

“…Furthermore, it can be assumed that the influence of feed present in the gastrointestinal tract on the absorption of orally administered drugs will not be the same for different drugs (Yu et al 1990;Baggot 1992;Sutter et al 1993). Previous studies with sulphadiazine and trimethoprim (Nielsen & Gyrd-Hansen 1994a) have shown that the bioavailability of these two compounds after oral administration to fasted pigs was 89% and 90%, respectively, versus 85% and 92% in the group of fed pigs. Thus the bioavailability was not significantly influenced by the presence of feed in the gastrointestinal tract.…”