Depletion of penicillin G residues in tissues, plasma and injection sites of market pigs injected intramuscularly with procaine penicillin G.

Procaine penicillin G was administered by intramuscular (i.m.) injection to groups of healthy 100 kg market pigs at the approved label dose (15,000 IU/kg body weight), once daily for three consecutive days; or an extra-label dose (66,000 IU/kg body weight), once daily for five consecutive days. Penicillin G residue depletion was followed in plasma, tissue and injection sites using a liquid chromatographic method. Groups of pigs were killed 1, 2, 3, 4, 5 and 8 days after the last injection with the label dose. Penicillin G was not detected in liver after 1 day of withdrawal, in muscle and fat after 2 days of withdrawal, in plasma after 4 days of withdrawal, in skin after 5 days of withdrawal, or in kidney and the injection sites after 8 days of withdrawal. Other groups of pigs were killed 1, 2, 3, 5 and 7 days after injection with the extra-label dose. In these pigs penicillin G was not found in liver after 2 days of withdrawal, in fat after 3 days of withdrawal, or in the muscle, skin, plasma and injection sites after 7 days of withdrawal. Penicillin G was found at all times in the kidneys of the groups of pigs that received the high dose. The technique used for neck injections was critical to obtain intramuscular rather than intermuscular injections. The Bureau of Veterinary Drugs, Health Protection Branch, Health Canada calculated that the appropriate withdrawal period for pigs was 8 days for a dose of 15,000 IU procaine penicillin G/kg body weight and 15 days for a dose of 66,000 IU/kg.

Disposition of penicillin G after administration of benzathine penicillin G, or a combination of benzathine penicillin G and procaine penicillin G in cattle.

Plasma concentration of penicillin G was evaluated in beef steers after administration of either a combination of benzathine penicillin G and procaine penicillin G in a 1:1 mixture at a dosage of 9,000 U/kg of body weight, IM (n = 5), 24,000 U/kg, IM (n = 5), or 8,800 U/kg, SC (n = 5), or benzathine penicillin G alone at a dosage of 12,000 U/kg, IM (n = 7). Plasma concentration of penicillin G was measured by use of a high-performance liquid chromatography assay that had a limit of determination of 0.005 microgram/ml. At a dosage for this combination of 9,000 U/kg IM, and 8,800 U/kg, SC, which are approved label recommendations in Canada, and the United States, respectively, mean (+/- SEM) peak plasma concentration was 0.58 (+/- 0.15) and 0.44 (+/- 0.02) microgram/ml, respectively. Although plasma penicillin concentration was quantifiable for 7 days in the steers that received 9,000 U/kg, IM, and for 4 days in the steers that received 8,800 U/kg, SC, the concentration was < 0.1 microgram/ml in both groups after the first 12 hours. After administration of the combination at dosage of 24,000 U/kg, IM, there was an initial peak plasma concentration at approximately 2 hours; thereafter, plasma concentration decreased slowly, with half-life of 58 hours. Although plasma penicillin G concentration was quantifiable for 12 days at this dosage, concentration was < 0.1 microgram/ml after the first 48 hours. After the initial 48 hours, plasma concentration of penicillin was of similar magnitude and decreased at similar rate for the combination at dosage of 24,000 U/kg and for 12,000 U/kg of benzathine penicillin G alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Depletion of penicillin G residues in tissues and injection sites of yearling beef steers dosed with benzathine penicillin G alone or in combination with procaine penicillin G.

The contribution of benzathine penicillin G to residues in tissues and injection sites of yearling beef steers was assessed by treating seven groups of five to seven steers with either benzathine and procaine penicillin G together or benzathine penicillin G alone. Steers were injected with a commercial combination of benzathine and procaine penicillin G according to the Canadian (intramuscular) or United States (subcutaneous) label dosages of 8600 and 8800 IU penicillin G/kg body weight, respectively. They were killed 14 or 30 days after the intramuscular injections, and 30 days after the subcutaneous injections. At the label withdrawal times, Canadian 14 days and United States 30 days, the levels in the injection sites for all of the treatments were 30-60 times above the Canadian and United States' Maximum Residue Limit of 50 micrograms/kg, while liver, kidney and gluteal muscle levels were below the Maximum Residue Limit. Other steers were injected intramuscularly with 24,000 IU benzathine/procaine penicillin G/kg body weight and slaughtered 8, 14 or 50 days after injection. Fifty-day injection site residues were 24 times the Maximum Residue Limit. Another group of steers was injected intramuscularly with benzathine penicillin G alone at 12,000 IU/kg body weight and slaughtered 14 days later. Penicillin G levels in the injection sites were 156 times the Maximum Residue Limit. The persistence of penicillin G residues at the injection sites in all the treatment groups appears to be attributable primarily to benzathine penicillin G. Visual inspection of muscle surfaces did not reliably reveal all injection site lesions in the underlying musculature.

Depletion of intramuscularly and subcutaneously injected procaine penicillin G from tissues and plasma of yearling beef steers.

Withdrawal periods required when doses of 24,000 IU and 66,000 IU of procaine penicillin G/kg body weight were administered to yearling beef steers by intramuscular injection daily for five consecutive days were investigated. These dosages are in excess of product label recommendations, but are in the range of procaine penicillin G dosages that have been administered for the treatment of some feedlot bacterial diseases. The approved dose in Canada is 7,500 IU/kg body weight intramuscularly, once daily, with a withdrawal period of five days. Based on the tissue residue data from this study, the appropriate withdrawal period is ten days for the 24,000 IU/kg body weight dose and 21 days for the 66,000 IU/kg body weight dose when administered intramuscularly to yearling beef steers. In a related study, 18 yearling beef steers received 66,000 IU of procaine penicillin G/kg body weight administered by subcutaneous injection, an extra-label treatment in terms of both dose and route of administration, typical of current practice in some circumstances. Deposits of the drug were visible at subcutaneous injection sites up to ten days after injection, with more inflammation and hemorrhage observed than for intramuscular injections of the same dose. These results suggest that procaine penicillin G should not be administered subcutaneously at high doses; and therefore a withdrawal period was not established for subcutaneous injection.

A study of the disposition of procaine penicillin G in feedlot steers following intramuscular and subcutaneous injection.

The disposition of an aqueous suspension of procaine penicillin G (300,000 U/mL) was studied in feedlot steers. Four groups of three steers were used. Steers in groups 1 and 2 received procaine penicillin G once daily for 5 days intramuscularly (i.m.) at a dose of 24,000 U/kg (group 1) or of 66,000 U/kg (group 2). The injection on the last day was administered in the gluteal muscle. Steers in group 3 (i.m. neck injection) and group 4 [subcutaneous (s.c.) injection] each received a single dose of procaine penicillin G at a dose of 66,000 U/kg. From every animal, after the last injection in groups 1 and 2 and following the single injection in groups 3 and 4, a series of blood samples was taken at fixed time intervals. The plasma from these samples was analysed for penicillin G by a high performance liquid chromatography (HPLC) assay in order to determine the disposition of penicillin. The maximum plasma concentration (Cmax) and the area under the curve (AUC) were significantly different between groups 1 and 2, but we found no difference in the disappearance rate constant between these two groups. Group 4 single s.c. injections produced a lower mean Cmax (1.85 +/- 0.27 microgram/mL) than the mean Cmax (4.24 +/- 1.08 micrograms/mL) produced in group 3 by i.m. injections into the neck muscle or the mean Cmax (2.63 +/- 0.27 microgram/mL) produced in group 2 by i.m. injections into the gluteal muscle. However the mean Cmax produced by i.m. injections into the neck muscles (group 3) was higher than the mean Cmax produced by i.m. injections into the gluteal muscle (group 2). Additionally, the disappearance t1/2 was longer (18.08 h) in group 4 following the s.c. injection and shorter (8.85 h) in group 3 following the i.m. neck injection, than the t1/2 following administration of the same dose i.m. into the gluteal muscle (15.96 h) in group 2. In this study, when procaine penicillin G was injected into the gluteal muscle, doses of 66,000 U/kg were necessary to produce plasma concentrations that were above a minimum inhibitory concentration (MIC) for penicillin G of 1.0 microgram/mL as compared to doses of 24,000 U/kg.

In vitro germicidal activity of teat dips against Nocardia asteroides and other udder pathogens.

Nine commercial teat dip formulations containing 1.94% linear dodecylbenzene sulfonic acid, or 1% available iodine from nonylphenoxypoly (ethyleneoxy) ethanol-iodine complex, or .5% chlorhexidine acetate were tested for contamination with aerobic and anaerobic bacteria and their in vitro germicidal activity against Staphylococcus aureus, Streptococcus agalactiae, Escherichia coli, and Nocardia asteroides. All products were free of bacteria when neutralized samples were tested on blood agar or liquid thioglycollate media. To test for in vitro efficacy, each teat dip preparation was mixed with a suspension of one of the pathogenic test organisms containing 10(8) bacteria/ml (final concentration) for .5 to 15 min. Viable bacteria were evaluated by direct plating of neutralized aliquots and by filtration techniques. All products were effective against E. coli, Staph. aureus, and Strep. agalactiae. With N. asteroides, the direct plating method gave equivocal results. The filtration experiments indicated that all teat dips containing dodecylbenzene sulfonic acid and nonylphenoxypoly (ethyleneoxy) ethanol-iodine complex were effective against all four pathogens. Three of the teat dips containing chlorhexidine acetate were ineffective against N. asteroides. The fourth teat dip, containing chlorhexidine acetate and an emollient, was partially effective.

Sweat sulfate concentrations are decreased in cystic fibrosis.

We have developed methods to measure inorganic sulfate in small volumes of sweat, and compared sulfate concentrations in sweat samples from CF patients and controls. In contrast to the increases in sweat chloride, sweat sulfate concentrations in 13 CF patients were reduced to 68 +/- 24% of control values (mean +/- SD, n = 25, p less than 0.001). Sulfate concentrations in sweat may depend on sweat rates, but the rates were not significantly different in the two study groups. Since we have observed a positive correlation between sweat sulfate and sweat chloride excretion in non-CF subjects in earlier studies, we suggest that the decreased sulfate in CF sweat may bear directly on the nature of the anion permeability defect present in the ductal epithelium of the CF sweat gland.

Determination of inorganic sulfate in human saliva and sweat by controlled-flow anion chromatography. Normal values in adult humans.

Following the previous demonstration that low concentrations of inorganic sulfate (SO4) in human serum and cerebrospinal fluid can be accurately determined by controlled-flow anion chromatography, the assay has been extended to the quantitation of free SO4 in saliva and sweat by modification of the established methods of sample collection and preparation. Salivary secretions were ultrafiltered to remove macromolecular polyanions that bind irreversibly to the anion-exchange separator column and reduce resolution. Sweat was collected from 22 fasted adult volunteers using a method which utilizes absorbent filter pads applied to the forearm after secretion had been stimulated by pilocarpine iontophoresis. It was necessary to acid wash the filter pads to reduce sulfate contamination. Saliva ultrafiltrate or sweat was diluted and injected onto a Dionex D-10 Ion Analyzer using the standard anion column system. The mean inorganic SO4 concentration in saliva from seventeen adult fasting volunteers was 72 +/- 4 mumol/l (+/- S.E.); the mean SO4 concentration in sweat was 83 +/- 3 mumol/l. Both are significantly less than in matching serum, suggesting that SO4 is actively removed during formation of these glandular secretions. The ion chromatographic assay is shown to be capable of measuring SO4 in biological fluids at concentrations that are otherwise undetectable by conventional assay techniques.

Parenteral nutrition in a premature infant with phenylketonuria.

Parenteral nutrition (PN) is now an important facet of the management of the extremely premature infant. However, its effects on those with inherited metabolic disease have not been well documented. We report an infant with classical phenylketonuria (PKU) who had unusually high serum phenylalanine at 12 days of life (5200 mumol; greater than 3.2 SD above our mean for PKU at 10-15 days of age) while on parenteral nutrition, despite a relatively high tolerance for phenylalanine on oral feeds at 3-4 months of life (97-128 mg/kg/day; normal for PKU: less than 90 mg/kg/day). Identification of PKU was somewhat delayed in this child because of failure to recognize that parenteral nutrition provides a phenylalanine load equivalent to or greater than the routine oral formula feeding. Despite the high levels of phenylalanine in the first 2 wk of life, mental and motor development are normal at 16 months of age. This case, the first such reported, suggests the parenteral nutrition in the premature PKU infant is relatively safe, but draws attention to the possible need for phenylalanine-free amino acid infusates for those who require long-term treatment.