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

Abstract

The disposition of spiramycin and lincomycin was measured after intravenous (i.v.) and oral (p.o.) administration to pigs. Twelve healthy pigs (six for each compound) weighing 16-43 kg received a dose of 10 mg/kg intravenously, and 55 mg/kg (spiramycin) or 33 mg/kg (lincomycin) orally in both a fasted and a fed condition in a three-way cross-over design. Spiramycin was detectable in plasma up to 30 h after intravenous and oral administration to both fasted and fed pigs, whereas lincomycin was detected for only 12 h after intravenous administration and up to 15 h after oral administration. The volume of distribution was 5.6 +/- 1.5 and 1.1 +/- 0.2 L/kg body weight for spiramycin and lincomycin, respectively. For both compounds the bioavailability was strongly dependent on the presence of food in the gastrointestinal tract. For spiramycin the bioavailability was determined to be 60% and 24% in fasted and fed pigs, respectively, whereas the corresponding figures for lincomycin were 73% and 41%. The maximum plasma concentration of spiramycin (Cmax) was estimated to be 5 microg/mL in fasted pigs and 1 microg/mL only in fed pigs. It is concluded that an oral dose of 55 mg/kg body weight is not enough to give a therapeutically effective plasma concentration of spiramycin against species of Mycoplasma, Streptococcus, Staphylococcus and Pasteurella multocida. The maximum plasma concentration of lincomycin was estimated to be 8 microg/mL in fasted pigs and 5 microg/mL in fed pigs, but as the minimum inhibitory concentration for lincomycin against Actinobacillus pleuropneumoniae and P. multocida is higher than 32 microg/mL a therapeutically effective plasma concentration could not be obtained following oral administration of the drug. For Mycoplasma the MIC90 is below 1 microg/mL and a therapeutically effective plasma concentration of lincomycin was thus obtained after oral administration to both fed and fasted pigs.

Pharmacokinetics of lincomycin following intravenousadministration in febrile goats

“…(Dumka and singh, 2013). High distribution of lincomycin to various tissues and body fluids were reflected by large Vd area which was higher than the Vd area in calves with induced Pasteurella haemolytica pneumonia (1.2 L/kg), buffalo calves (1.15 L.kg -1 ), pigs (1.1 L.kg -1 ) cats (0.97-1.24 L.kg -1 ) and chicken (1.76 L.kg -1 ) for lincomycin (Burrows et al 1986;Nielsen and Gyrd-Hansen 1998;Albarellos et al 2012Albarellos et al , 2013Gouri et al 2014;El-Sayed et al 2015). In support of present result, Vd area of florfenicol in febrile calves (2.11± 0.18 L/kg) was reported by Dumka and Singh, (2013).…”

“…Lincomycin standard (lncomycin hydrochloride, CDH, Delhi) was procured commercially. The drug was estimated using HPLC (Perkin Elmer, series 200) by reverse-phase chromatography (Nielsen and Gyrd-Hansen 1998). The system conditions included analytical C18 column (particle size 5 µ, 4.6×250 mm, Waters, USA), acetonitrile as mobile phase A (25%), phosphate buffer as mobile phase B(75%), flow rate of 1 ml/ min, UV/VIS detector set at 210 nm as per the details mentioned in the published report of Nielsen and Gyrd-Hansen, (1998) for estimation of drug and Total Chrome software (version 6.1) for instrument control and data analysis.…”

“…Successful treatment of arthritis and pedal osteomyelitis usually associated with Trueperella pyogens (Arcanobacterium pyogens) has been reported with lincomycin in sheep (Giguere, 2013). Pharmacokinetics of lincomycin has been conducted in dairy cattle (Weber et al1981), calves (Burrows et al 1983(Burrows et al , 1986, buffalo calves (Gouri et al 2014), pigs (Chaleva and Nquyen 1987;Nielsen and Gyrd-Hansen 1998), cats (Albarellos et al 2012(Albarellos et al , 2013 and chickens (El-Sayed et al 2015). Further, disease conditions are known to alter the disposition of antimicrobials (Kumar et al 2010;Burrows 1986).…”

The effect of soybean oil refuse powder used as vehicle on the absorption of oxolinic acid in chickens under fasting and nonfasting conditions and the correlation with in vitro dissolution

“…The T max and MRT t values observed under fed conditions were shorter than those under fasting conditions, and C max was increased by the existence of food. It is well known that the bioavailability of a drug product is affected by food in humans and animals (Winstanley & Orme, 1989; Nielsen & Gyrd‐Hansen, 1994, 1996, 1998; Campbell & Rosin, 1998). It has been variously reported that bioavailability after oral drug administration to humans or animals was increased, decreased or not changed by food intake.…”

Effect of composition and quality of diet and feeding time on the kinetics and efficacy of some anthelmintic drugs: A mini-review

“…In animals, the kinetics and activity of several antimicrobial drugs are also influenced by the quality and quantity of food (e.g. Abdullah and Baggot, 1986;Nielsen and Gyrd-Hansen, 1998).…”