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J L Riond

Publications and source records attributed to J L Riond.

51 records · Page 3Linked to original sources

Influence of dietary citric acid and calcium on the bioavailability of orally administered chlortetracycline in piglets.

In a study involving 18 piglets divided into three groups (A, B and C), the effects of dietary calcium and citric acid, and feeding technique on chlortetracycline bioavailability were examined. Groups of 6 animals received a basal diet with either 0.7% (group A) or 1.4% calcium (groups B and C). Citric acid was not included in diets of the first experimental period. In the second period, either 1.5% (groups A and B) or 3.0% (group C) citric acid was added to the diet. In both experimental periods, chlortetracycline was administered once intravenously (7.5 mg/kg b.w.) and once orally (30 mg/kg b.w.). After each administration, blood samples were taken at regular intervals in order to determine chlortetracycline serum concentrations by a microbiological method. Following oral chlortetracycline intake, low dietary calcium or citric acid addition to the diet produced increased chlortetracycline serum concentrations. Chlortetracycline bioavailability was 12.6% at 0.7% dietary calcium, and 9.5% at 1.4% dietary calcium. Enteral chlortetracycline absorption was improved 65% with 1.5% or 3.0% dietary citric acid supplementation. An 8-hour delay of feed intake following oral chlortetracycline intake did not significantly influence chlortetracycline bioavailability.

Administration, Oral↗

Bovine viral diarrhea virus-induced cerebellar disease in a calf.

Bovine viral diarrhea virus (BVDV) was isolated from buffy coat cells of a 10-day-old calf with signs of cerebellar disease--ataxia, hypermetria, and intention head tremor. The tentative diagnosis was BVDV-induced cerebellar hypoplasia. At necropsy, gross lesions were not identified. Histologic findings suggested BVDV-induced diffuse hypomyelination throughout the CNS, as reported in the United Kingdom and The Netherlands.

Animals↗

Allometric analysis of doxycycline pharmacokinetic parameters.

Doxycycline serum concentration-time profiles and elimination half-lives in several species were evaluated by allometric techniques. Doxycycline elimination half-life increased with body weight. Interspecies scaling of total or free doxycycline serum concentration-time profiles was possible by use of Dedrick plots with the exception of doxycycline total concentrations in cats. The observed difference in cats was attributed to more extensive binding to plasma proteins.

Animals↗

Comparative pharmacokinetics of doxycycline in cats and dogs.

The disposition of doxycycline hyclate was studied in six adult mixed-breed female cats and six adult mid-sized female dogs following a single intravenous administration of 5 mg/kg body weight. Doxycycline volume of the central compartment, area volume of distribution, volume of distribution at steady state, and total body clearance were significantly smaller in cats. The differences were attributed to more extensive binding of doxycycline to plasma protein including albumin in cats. The significant differences in the volume of distribution and total body clearance were not reflected in elimination half-lives under the conditions of this study (sample size, inhomogeneous population). Doxycycline elimination half-life was 4.56 +/- 0.68 (SEM) h for cats and 6.99 +/- 1.09 h for dogs. Dosage regimens recommended in the veterinary literature were evaluated by the computer program PETDR.

Animals↗

Pharmacokinetics and metabolic inertness of doxycycline in young pigs.

The disposition of doxycycline hyclate after IV administration of 20 mg/kg of body weight was studied in 6 pigs. Median elimination half-life, estimated in 4 pigs, was 3.92 hours. Mean (+/- SEM) total body clearance was 1.67 +/- 0.18 ml/min/kg, and mean apparent volume of distribution at steady state was 0.53 +/- 0.04 L/kg. In 2 pigs, secondary peaks in the logarithmic serum concentration-time profile suggested discontinuous enterohepatic cycling, and precluded using these pigs in the pharmacokinetic analysis. The extent of doxycycline binding to serum protein was 93.1 +/- 0.2%. Serum or urine from 3 of the pigs was analyzed by use of photodiode array detection and mass spectrometry of a high-performance liquid chromatographic column effluent. These procedures documented lack of doxycycline biotransformation in pigs. It is concluded that, despite an elimination half-life shorter than that reported in other species, doxycycline may be a valuable antimicrobial drug for use in swine practice, pending the development of appropriate formulations.

Animals↗

Determination of doxycycline in bovine tissues and body fluids by high-performance liquid chromatography using photodiode array ultraviolet-visible detection.

A sensitive and selective high-performance liquid chromatographic assay was developed to quantitate doxycycline concentrations in bovine tissues and body fluids. The method involved sonication of doxycycline-spiked minced tissues with appropriate solutions to extract tissue-bound drug. Acetonitrile:85% phosphoric acid:water (20:2:78) was added to doxycycline-spiked serum or urine. The mixtures were ultrafiltered through 30,000 or 10,000 Da molecular weight cutoff microseparation systems. Separation was obtained by a reversed-phase microbore column. Absorbance of the column effluent was measured by an ultraviolet-visible photodiode array detector scanning from 235 to 380 nm and/or a photometric detector operated at 268 or 345 nm. Chromatographic peak homogeneity was evaluated by three-dimensional spectrochromatograms, contour maps, and absorbance ratios.

Animals↗

Doxycycline binding to plasma albumin of several species.

The affinity of doxycycline for crystalline plasma albumin fraction V, originating from sheep, dogs, cats, cows, pigs and humans, was evaluated by means of double-reciprocal and Scatchard plots. Mathematical modelling and weighted least-squares non-linear regression analysis of each Scatchard plot identified one binding component characterized by one high affinity binding site, and a second component attributed to non-specific binding to albumin. Association constants for this binding site ranged from 38,471 +/- 13,369 (SEM) l/mol for the interaction of doxycycline with ovine albumin to 6405 +/- 2375 l/mol for the interaction of doxycycline with human albumin. Statistical evaluation of the results suggested slight species-related differences in the values of association constants. Diphenylhydantoin, phenobarbital or carbamazepine did not displace doxycycline from binding sites on bovine albumin.

Animals↗

Pharmacokinetics and metabolic inertness of doxycycline in calves with mature or immature rumen function.

The pharmacokinetic determinants of doxycycline were calculated after a single IV administration of the drug (20 mg/kg of body weight) in 5 Angus calves with mature rumen function and 4 Holstein calves with immature rumen function. Doxycycline disposition was best described by means of an open 2-compartment model. Median elimination half-life was 14.17 hours (Angus) and 9.84 hours (Holstein). Mean (+/- SEM) total body clearance was 1.07 (+/- 0.06) and 2.20 (+/- 0.21) ml/min/kg in Angus and Holstein calves, respectively. Mean extent of doxycycline binding to serum proteins was 92.3% (+/- 0.8%). The large steady-state volume of distribution (1.31 +/- 0.11 L/kg in Angus and 1.81 +/- 0.24 L/kg in Holstein calves), despite the small free fraction in serum, suggested a relatively unrestricted access of drug into the intracellular compartment and/or appreciable tissue binding. Results of mass spectrometric analysis of serum and urine from calves administered doxycycline IV revealed absence of biotransformation, because only parent drug could be detected. Thus, doxycycline may be a valuable antibiotic for use in food animals pending further studies on tissue residues, safety, and efficacy.

Animals↗

Pharmacology and toxicology of doxycycline.

Doxycycline, a structural isomer of tetracycline, has been used in human medicine since 1966. The molecule, obtained semi-synthetically from oxytetracycline or methacycline, is highly lipophilic permitting excellent penetration into tissues. In vitro antimicrobial activity of doxycycline is superior to that of the older tetracyclines (chlortetracycline, oxytetracycline, tetracycline). In laboratory animals, the protective dose for 50% of the subjects (PD50) demonstrates a better in vivo activity than that of all other members of the tetracycline family. Clinical use in human medicine has confirmed the efficacy of doxycycline for a variety of infectious conditions. High lipophilicity results in a large volume of distribution, substantial binding to plasma proteins, and reabsorption in the renal tubules and gastrointestinal tract, thereby conferring a long elimination half-life to the drug. Excellent absorption after oral administration allows small oral doses and minimizes the known side effects of tetracyclines on the gastrointestinal tract--irritation and suprainfection. The contrast to the other tetracyclines, doxycycline does not accumulate in renal failure due to a compensatory gastrointestinal secretion. The pharmacology, toxicology and therapeutics of doxycycline in laboratory animals and man indicate that this drug may be a valuable antimicrobial for use in veterinary medicine.

Animals↗

Prediction of pharmacokinetic profiles of ampicillin sodium, gentamicin sulfate, and combination ampicillin sodium-gentamicin sulfate in serum and synovia of healthy horses.

Pharmacokinetics of ampicillin sodium (11 mg/kg), gentamicin sulfate (2.2 mg/kg), and combination ampicillin sodium-gentamicin sulfate were determined for serum and synovia of healthy horses given single-dose IV injection and were not found to be different from those from other reports; however, a prolonged terminal gamma-phase for gentamicin (8,498 +/- 1,842 minutes) in serum of horses was found to exist. Pharmacokinetic interaction between combination ampicillin sodium-gentamicin sulfate was not observed int he serum or synovia. Prediction of ampicillin sodium or gentamicin sulfate concentrations in synovia, based on serum-based pharmacokinetics, cannot be accomplished solely upon analysis of peripheral-compartment pharmacokinetics. However, once equilibrium is achieved between synovia and extracellular fluid in the peripheral compartment, the decrease in drug concentrations in synovia parallels that in serum. Therefore, after 6 hours, synovial concentrations of gentamicin sulfate can be predicted based on peripheral-compartment pharmacokinetics, using an appropriate correction factor. The significance of these findings need to be correlated with clinical conditions so that a pharmacostatistical model for the prediction of synovial concentrations of drug(s) during treatment of horses with septic arthritis can be developed.

Ampicillin↗

Influence of thyroid function on the pharmacokinetics of gentamicin in pigs.

Hypothyroidism or hyperthyroidism was induced in 10 pigs (5 pigs/group) and each pig was administered gentamicin (6 mg/kg of body weight, IV). Low thyroxine and triiodothyronine resulted in a decrease in creatinine clearance (P = 0.04), an increase in serum creatinine concentration (P = 0.003), and a decrease in gentamicin systemic clearance (P = 0.002), compared with findings in control pigs (n = 5). These effects probably were secondary to a decreased glomerular filtration rate associated with hypothyroidism. A strong correlation among the 3 treatment groups was found between gentamicin systemic clearance and creatinine clearance (r = 0.72; P = 0.004) and between gentamicin systemic clearance and serum creatinine concentration (r = -0.77; P = 0.0007). Hyperthyroidism induced a slight but significant decrease in protein binding (P = 0.002). However, the significant changes in the hypothyroid pigs and the hyperthyroid pigs were not of a magnitude sufficient to alter gentamicin elimination half-life. Gentamicin disposition was best described, with a 4-compartment open model.

Analysis of Variance↗