[We must become louder (interview by Urs Luthi)].
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Biomedical subjects
K Küng
Publications and source records attributed to K Küng.
Sprayed medicated feed with sulfadimidine for piglets.
The bioavailability of two different forms of medicated feed containing 2000 mg sulfadimidine (SDM) per kg was determined in three groups of eight piglets. In the first group, pharmacokinetic parameters of SDM were determined after a single intravenous dose of 10 mg/kg body weight and after single oral doses of 45 mg/kg body weight ingested either as an oleus solution sprayed directly onto the feed pellets ready for use (SPR) or as a commercially available premix incorporated into the feed before pelletising (PMX). After the single intravenous administration, the mean +/- SD of the volume of distribution was 0.34 +/- 0.05 l/kg, the total body clearance 0.37 +/- 0.07 ml/min.kg, the mean residence time 15.5 +/- 2.5 h, and the elimination half-life 11.1 +/- 2.0 h. Although no statistical significance existed, a single meal with PMX was associated with slightly higher mean values for the maximum serum concentration (Cmax), the time to reach Cmax, and the bioavailability (52.98 +/- 6.60 micrograms/ml, 6.8 +/- 1.1 h, 59.7 +/- 12.1%, respectively, vs. 40.04 +/- 13.19 micrograms/ml, 6.0 +/- 1.4 h, 49.0 +/- 18.6 for SPR). The remaining two groups of piglets received medicated feed with either SPR or PMX during a 3-day period both with restrictive (twice-daily) or ad libitum feeding according to a cross-over design. In all four cases, potentially efficacious plasma SDM concentrations between 50 and 150 micrograms/ml were obtained within 24 h after initiation of the treatment. With PMX, plasma concentrations tended to be higher than with SPR with both feeding regimens. Ad libitum feeding was associated with a significantly higher food intake and hence a higher SDM intake resulting in higher plasma concentrations. Additionally, plasma concentrations were more constant over time with ad libitum feeding whereas they declined considerably between meals in restrictively fed animals. In vitro dissolution tests of the two types of medicated feed revealed that SDM was rapidly released from SPR (58% within 15 min) and that SDM release from PMX was markedly slower (3% within 15 min). Despite the relatively slow rate of in vitro dissolution, in vivo absorption of SDM was satisfactory. It is concluded that both forms of SDM medicated feed may be considered bioequivalent and potentially efficacious in piglets.
Administration, Oral↗
Clarithromycin pharmacokinetics after oral administration with or without fasting in crossbred beagles.
Clarithromycin was administered to eight dogs intravenously and orally. A suspension or a tablet was given to animals both immediately after feeding and on an empty stomach. Neither the formulation nor the time of administration in relation to feeding significantly influenced the pharmacokinetic parameters. The lowest mean (+/-SD) maximum plasma concentration (Cmax) of 3.0 +/- 0.6 micrograms/ml, the lowest bioavailability (F) of approximately 69 per cent and the shortest time above the proposed breakpoint of susceptibility (L) of 2.9 +/- 1.3 hours were observed with the suspension after feeding. The highest Cmax of 3.6 +/- 0.8 micrograms/ml, the highest F of 83 per cent and the longest L of 4.5 +/- 2.0 hours were observed with the suspension in the fasted group. The mean time at which Cmax occurred (tmax) was between one and two hours after administration. In conclusion, clarithromycin is potentially suitable for therapeutic use in dogs, pending species-specific studies of safety and therapeutic efficacy.
Administration, Oral↗
Parathyroid hormone-related protein and calcium concentrations in milk and blood of ewes.
Parathyroid hormone-related protein (PTHrP) and calcium (Ca) concentrations were measured 2 to 3 months postpartum in milk and plasma or serum of 22 ewes by the use of commercial radioimmunoassay kits for PTHrP concentration, colorimetry for serum total Ca concentration (Catot), and atomic absorption spectrophotometry for milk total Ca concentration. Scatter plots did not reveal dependency between milk Ca and Catot, Catot and plasma PTHrP, milk Ca and milk PTHrP, and milk PTHrP and plasma PTHrP. Thus, the systemic and mammary effects of PTHrP are not major determinants of the endocrine, paracrine, and autocrine regulation of Ca homeostasis during lactation in ewes.
Animals↗
Effect of the interval between feeding and drug administration on oral ampicillin absorption in dogs.
Eight dogs of various breeds received single oral doses of 20 mg/kg bodyweight ampicillin at four different time intervals relative to feeding a meal. In treatment A the dogs were fasted for 12 hours before and after ampicillin administration. In treatment B the dogs received ampicillin immediately after, in treatment C one hour before and in treatment D two hours after the meal. Each dog received these treatments during a period of feeding dry and canned dog food according to an 8 x 8 Latin square design. Blood samples were taken at specified time intervals after drug administration by jugular venepuncture. Antibiotic concentrations in plasma were determined by microbiological assay. Non-compartmental pharmacokinetic parameters were calculated from the individual concentration-time curves and were compared by non-parametric statistic tests between treatments and types of food. With both dry and canned food ampicillin absorption was impaired when the drug and food were given at the same time (treatment B) as compared to the absorption in fasting dogs (treatment A and C). On dry food, drug absorption was also decreased in treatment D. It is recommended for clinical purposes to give ampicillin to fasted dogs, and to wait at least one hour before feeding. After a meal (dry food) waiting two hours until drug administration is not sufficient to avoid impaired ampicillin absorption.
Administration, Oral↗
Bioavailability of different forms of amoxycillin administered orally to dogs.
Amoxycillin was administered to six dogs intravenously (as the sodium salt at 20 mg/kg bodyweight) and orally (as the trihydrate at 20 mg/kg). The oral treatments followed a Latin square pattern, each dog receiving amoxycillin as a 60 ml suspension by stomach tube, or as 3 ml of drops or in the form of tablets. The concentration of the drug in the plasma was measured microbiologically and its pharmacokinetic parameters were calculated by the use of statistical moments. After intravenous administration the mean +/- sd apparent volume of distribution was 0.312 +/- 0.102 litre/kg, the steady state rate of clearance was 3.4 +/- 1.1 ml/min/kg and the mean residence time was 1.6 +/- 0.4 hours. After oral administration the liquid forms of the drug tended to be more readily absorbed than the tablets, as indicated by their higher bioavailabilities (suspension 76.8 +/- 16.7 per cent, drops 68.2 +/- 25.8 per cent, tablets 64.2 +/- 17.9 per cent). However, the differences between their pharmacokinetic parameters were not statistically significant. The respective values of Cmax for the tablets, drops and suspension were 18.6 +/- 5.3 micrograms/ml, 18.1 +/- 2.4 micrograms/ml and 20.7 +/- 2.2 micrograms/ml, of tmax 2.0 +/- 1.0 hours, 1.4 +/- 0.6 hours and 1.4 +/- 0.5 hours and of the AUC 69.5 +/- 22.5 micrograms/ml hours, 71.8 +/- 21.0 micrograms/ml hours and 80.6 +/- 21.8 micrograms/ml hours. The two useful drug products (drops and tablets) had similar pharmacokinetic profiles in the dogs and can therefore be regarded as equivalent in this species.
Administration, Oral↗
Pharmacokinetics of sulphadoxine and trimethoprim in sows: influence of lactation.
A potentiated sulpha drug was administered intravenously to 12 sows on the 17th day of lactation and to 4 sows in early pregnancy to study the influence of lactation on its disposition kinetics. The dose-rate of sulphadoxine (SDX) used was 12 mg/kg b.w. while that of trimethoprim (TMP) was 2.4 mg/kg b.w. The pharmacokinetic parameters of SDX showed no significant difference between lactating and pregnant sows (Vss, 0.24 +/- 0.04 L/kg; Cls, 0.25 +/- 0.05 ml/min per kg: MRT, 17.08 +/- 4.48 h). SDX did not accumulate in milk, the concentrations in milk being less than the concentrations in serum at the same time. Of the pharmacokinetic parameters for TMP, only the mean residence time was significantly different between the two groups (Vss, 1.60 +/- 0.31 L/kg; Cls, 4.62 +/- 1.07 ml/min per kg: MRTlactating, 5.43 +/- 1.26 h; MRTpregnant, 7.74 +/- 1.72 h). TMP was excreted in milk to a considerable extent, the ratio of its concentration in milk to that in serum at the same time being over 2.2. These two substances show a completely different pharmacokinetic behaviour. Even though TMP is excreted more quickly in lactating sows, adjusting the dose of this potentiated sulpha drug does not seem to be appropriate.
Animals↗
[Pharmacokinetics of baytril (enrofloxacin) in dogs].
Baytril with the active ingredient enrofloxacin was given to four dogs in a single intravenous and oral dose of 5 mg/kg body weight. Measured plasma concentrations were different depending on the method of analysis used. Using high performance liquid chromatography quantitative determination of both enrofloxacin and its main metabolite ciprofloxacin is possible whereas antimicrobially active substance is measured by bioassay. Ciprofloxacin occurred early in the concentration-time curves after intravenous and oral administration of the parent drug enrofloxacin with cmax 0.2 and 0.3 microgram/ml, respectively, at tmax 2 and 4 h, respectively. Areas under the curve (AUC) calculated from concentration-time-curves with bioassay data are overestimated, because ciprofloxacin may be more active than enrofloxacin against E. coli 14 (ICB 4004) used in this test. Thus, pharmacokinetic parameters which are derived from AUC-values are overestimated, too. Oral bioavailability calculated with bioassay results was more than 100% whereas availability of enrofloxacin was only 53%. Clearance was 10.3 ml/min.kg (antimicrobially active substance) and 27.1 ml/min.kg (enrofloxacin). Elimination half life was 3.7 and 2.4 h, respectively.
Administration, Oral↗
Comparison of an HPLC and bioassay method to determine antimicrobial concentrations after intravenous and oral administration of enrofloxacin in four dogs.
Plasma samples of dogs given 5 mg kg-1 bodyweight of a broad spectrum antimicrobial with the active ingredient enrofloxacin were assayed by two different methods (bioassay: Escherichia coli 14 ICB 4004 on ISO sensitest agar; high performance liquid chromatography with a RP C18 column). At concentrations up to 1000 ng ml-1 a linear correlation between values obtained by the two assay methods was found. At concentrations above 1000 ng ml-1 no correlation could be determined. The main metabolite of enrofloxacin, ciprofloxacin, is an important determinant of overall antimicrobial activity and hence influences bioassay results.
Administration, Oral↗
Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin after intravenous and oral administration of enrofloxacin in dogs.
Four dogs were given 5 mg/kg body weight enrofloxacin intravenously (i.v.) and orally (p.o.) in a cross-over study. Plasma concentrations of the active ingredient enrofloxacin and its main metabolite ciprofloxacin were determined by a reversed phase liquid chromatographic method. Pharmacokinetic parameters of both substances were calculated by use of statistical moments and were compared to those of enrofloxacin described in the veterinary literature. Mean enrofloxacin t1/2 lambda z was 2.4 h, mean Cls was 27.1 ml/min.kg, and mean Vss was 7.0 l/kg. After i.v. and p.o. administration, concentrations of ciprofloxacin exceeding minimal inhibitory concentrations of several microorganisms were reached (Cmax = 0.2 microgram/ml, tmax = 2.2 h after intravenous administration; Cmax = 0.2 microgram/ml, tmax = 3.6 h after oral administration). A considerable part of the antimicrobial activity is due to ciprofloxacin, the main metabolite of enrofloxacin.
Administration, Oral↗