Percutaneous absorption and excretion of xenobiotics after topical and intravenous administration to pigs.

Interspecies comparisons suggest that the weaning pig is a suitable surrogate for man in percutaneous absorption studies. Despite known anatomical and physiological similarities between porcine and human skin, very few investigations of percutaneous absorption phenomena have been conducted in pigs. This study examined radiolabel excretion patterns after intravenous (iv) and topical administration of six 14C-radiolabeled compounds in weanling Yorkshire sows.

Estimation of physiological volumes in the isolated perfused porcine skin flap.

A requirement for pharmacokinetic modeling of isolated perfused organ systems used for in vitro to in vivo extrapolations is a measure of the organ's physiological spaces. Two methods were employed to estimate intravascular and extracellular spaces in four isolated perfused porcine skin flaps (IPPSF) from 2 pigs. One of these methods used regression techniques based on a one-compartment model, and was found to be a good estimator of intravascular volume only.

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.

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.

Kluyver's work in retrospect: wisdom of foresight? Lecture delivered on October 27, 1988 before The Netherlands Society for Microbiology in commemoration of the birthday of Prof. dr. ir. A.J. Kluyver (1888-1956).

In this paper three former students of Kluyver look back upon his work and make an effort to assess its significance in the development of present-day microbiology.

Definition of a physiologic pharmacokinetic model of cutaneous drug distribution using the isolated perfused porcine skin flap.

A physiologic pharmacokinetic model describing drug disposition in the isolated perfused porcine skin flap (IPPSF) is derived. The IPPSF is well suited for experimental studies of dynamic drug distribution into skin because arterial and venous drug fluxes can be continuously monitored. The system parameters of the model are uniquely identifiable and describe the cutaneous efflux profile as a function of arterial input flux and tissue partitioning or extraction.

The isolated perfused porcine skin flap. III. Percutaneous absorption pharmacokinetics of organophosphates, steroids, benzoic acid, and caffeine.

The isolated perfused porcine skin flap (IPPSF) has been developed as an alternative in vitro tool for examining the pharmacokinetics and mechanisms of percutaneous absorption. In this study, dosing solutions of seven 14C-radiolabeled compounds representing three chemical classes--organic acid/base [benzoic acid (B), caffeine (C)], organophosphate (OP) pesticides (diisopropylfluorophosphidate, malathion, parathion), and steroid hormones (progesterone, testosterone)--were prepared in ethanol and applied topically at a surface concentration of 40 micrograms cm-2 to the IPPSF. A three-compartment pharmacokinetic model used to stimulate mass transfer from the surface (C1), diffusion through epidermis and dermis (C2), and transfer into the capillary perfusate (C3), was developed based on flux through the IPPSF from 0 to 8 hr.

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.

In vivo and in vitro metabolism of benzo(a)pyrene by the larva of the newt, Pleurodeles waltl.

1. The larva of the amphibian species, Pleurodeles waltl was shown to metabolize benzo(a)pyrene in vivo into a variety of oxidized products. 2.

Pharmacokinetic estimation for therapeutic dosage regimens (PETDR)--a software program designed to determine intravenous drug dosage regimens for veterinary applications.

Pharmacokinetic estimation for therapeutic dosage regimens (PETDR) is a soft-ware program used to design individualized intravenous dosage regimens, determine concentration-time profiles, predict serum concentrations at a specific time after intravenous dosing and predict the time after the last dose to achieve a specified concentration of drug. The reference pharmacokinetic parameters may be based on an individual animal's pharmacokinetic disposition of drug or on FARAD (Food Animal Residue Avoidance Databank) mean population kinetic parameters. An individual animal's kinetic parameters may be input for predetermined analysis or the program can calculate these values by input of raw serum concentration-time data.

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).

Effects of chemical pollution on the activities of hepatic xenobiotic metabolizing enzymes in fish from the River Rhône.

Polychlorobiphenyl (PCBs) levels and hepatic xenobiotic metabolizing enzyme activities were measured in fish from three locations of the River Rhône to study the consequences of a constant loading of PCBs from a PCB incineration plant. Our results show that levels of PCBs and enzyme activities were higher in fish living downstream from the plant than in fish from two locations upstream, suggesting enzyme induction by PCBs (known to be potent inducers in laboratory conditions). Enzyme activities were studied in spring and autumn in three species: nase (Chondrostoma nasus), roach (Rutilus rutilus) and grayling (Thymallus thymallus).

Aflatoxin-impaired ability to accumulate oxycarotenoid pigments during restoration in young chickens.

The mechanism by which aflatoxin causes paling in chickens was investigated by measuring its effect on the restoration of pigments in 3-wk-old birds made pale by feeding a white corn-soy diet. Pigment restoration was accomplished by feeding the same diet supplemented with lutein (70 micrograms/g of diet), which is the major oxycarotenoid pigment in chicken diets and tissues. The oxycarotenoids (free, monoester, and diester forms of lutein) in the toe web, liver, serum, and jejunal mucosa of control and aflatoxin-fed (2 micrograms/g of diet) birds were measured by HPLC at 0, 1, 2, 3, 6, and 9 days of repletion.

Coarctation of the abdominal aorta.

Coarctation of the abdominal aorta constitutes a rare group of vascular abnormalities, including segmental stenoses and extended hypoplasia. Hypertension is the usual solitary clinical finding and contrasts with the diversity of anatomic lesions and surgical techniques used for treatment. It is often difficult to determine whether the lesion is congenital or due to Takayasu's aortitis.

Gentamicin pharmacokinetics and nephrotoxicity in naturally acquired and experimentally induced disease in dogs.

Pharmacokinetic disposition of gentamicin was studied in 69 dogs--12 control and 33 subtotally nephrectomized dogs representing combined data from previous experimental studies, and 24 dogs with a variety of diseases and degrees of renal dysfunction. Drug disposition varied considerably within and between diseases, and dosages had to be altered to achieve therapeutic drug concentrations and to minimize drug toxicosis. Decreased drug clearance when serum creatinine and urea nitrogen concentrations are normal may be indicative of subclinical renal disease and therefore may indicate a predisposition for development of nephrotoxicosis.

[Anorexia nervosa and pregnancy].

We report the case of a pregnancy associated with severe anorexia nervosa. The patient weighed 33 kg for 1 m 51 at conception. The pregnancy was obtained during a spontaneous cycle.

Gentamicin dosing strategies for dogs with subclinical renal dysfunction.

Twenty-six subtotally nephrectomized dogs were used as a model for subclinical renal dysfunction to evaluate the nephrotoxic potential of gentamicin administered according to four different dosage regimens. Dosages were individualized based on the pharmacokinetic disposition of drug in each dog. Gentamicin at 3.