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Biomedical subjects

W L Hayton

Publications and source records attributed to W L Hayton.

At least 19 recordsLinked to original sources
PubMed1994

Body size and the toxicokinetics of trifluralin in rainbow trout.

Rainbow trout (Oncorhynchus mykiss) ranging from 0.2 to 3395 g were exposed to trifluralin (TF) in water at concentrations of 0.6-2.0 micrograms/liter. Trout of all body sizes rapidly accumulated TF from the water. The uptake clearance (P, ml hr-1g-1) of TF from the water decreased as body weight (BW, g) increased. This decrease followed the allometric equation P (ml/hr) = 182.BW0.66. Other kinetic parameters affected by body size were the steady-state volume of distribution which had a BW exponent value of 1.07 and the biological half-life which increased in larger fish. The relatively larger volume of distribution in larger fish reflected an increased capacity for TF in peripheral compartment-associated tissues. Metabolic elimination and the bioconcentration factor of TF did not change systematically with changes in body size. Variation in total body lipid content could not adequately explain the increase in peripheral storage capacity for TF; the decreased plasma protein binding that was observed in larger trout may also have been involved.

Animals↗
PubMed1991

Pharmacokinetics of intravenous cefetamet and oral cefetamet pivoxil in children.

The pharmacokinetics of cefetamet were determined after intravenous (i.v.) administration of cefetamet and oral administration of cefetamet pivoxil syrup to patients between the ages of 3 and 12 years. The patients were hospitalized for reconstructive urological surgery; to prevent infection, prophylactic i.v. cefetamet was administered on the day of surgery and oral cefetamet pivoxil was administered 2 days later. After i.v. administration, the mean (+/- standard deviation) half-life of cefetamet was 1.97 +/- 0.60 h (n = 18), which was different from the 2.46 +/- 0.33 h reported for nine adults (22 to 68 years old) in a previous study. The average values for the mean residence times were 2.35 +/- 0.94 and 2.83 +/- 0.34 h and the average values for the fraction of the dose eliminated unchanged in the urine were 79.9% +/- 8.99% and 80% +/- 11% in children and adults, respectively. Plots of mean systemic clearance and steady-state volume of distribution versus body weight for the children and comparative adults were linear on log-log coordinates, and the slopes of the plots were 0.661 and 0.880, respectively. These slope values suggested that mean systemic clearance values per unit of body surface area were similar in children and adults and that maintenance doses for children should be the adult maintenance dose multiplied by the child's surface area divided by 1.73 m2. The mean (+/- standard deviation) oral bioavailabilities of cefetamet pivoxil were 49.3% +/- 15.7% in 3- to 7-year-old children who received a 500-mg dose and 37.9% +/- 10.0% in 8- to 12-year-old children who received a 1,000-mg dose. These values were not different from that observed in the adult group after two 500-mg tablets. Likewise, the peak concentration of cefetamet in plasma and its time of occurrence in children were in line with the values which have been observed for adults.

Administration, Oral↗
PubMed1991

Chronic ethanol consumption causes increased glucuronidation of morphine in rabbits.

1. Male rabbits were given an i.p. injection of 15 mg/kg morphine and plasma concentrations of morphine and morphine-3-glucuronide (M3G) were simultaneously quantified by h.p.l.c. After 14 days of 10% ethanol in the rabbits' drinking water, a second injection of morphine was administered and plasma concentrations were determined again. 2. Morphine plasma clearance increased significantly by 42% after ethanol treatment. The area under the plasma concentration time curve (AUC) for morphine decreased by 23% while the AUC for the glucuronide increased by 22%. 3. The ratio of the AUCs (glucruonide/morphine) increased by 72%. These results demonstrate that chronic ethanol treatment of rabbits results in increased clearance of morphine after an i.p. dose. The increase in clearance is most likely due to induction of UDP-glucuronosyltransferase isozymes by ethanol.

Animals↗
PubMed1990

Paraquat pharmacokinetics using a subcutaneous toxic low dose in the rat.

The pharmacokinetics of paraquat were examined at a dose which produced lung disease but avoided renal damage. Following single sc injections of 14CH3-paraquat (72 mumols/kg) in male Sprague-Dawley rats, blood was sampled via indwelling jugular cannulas. Noncannulated rats were exsanguinated by cardiac puncture during a 7-day test period. Blood, liver, kidney, lung, brain, heart, spleen, gi tract, injection site, adrenals, body, urine, and feces were analyzed for total radioactivity. Histology of lung after 7 days revealed (+1) paraquat lung disease. No evidence of renal damage was observed. Paraquat was rapidly absorbed. Peak blood concentrations of 58 nmol/ml were measured at 20 min. Peak lung and kidney paraquat concentrations at 40 min were 65 and 359 nmol/g, respectively. Paraquat pharmacokinetics (NONLIN) were best described by a two-compartment open model; the mean biological half-life was 40.9 hr. Eighty-five percent of the dose was eliminated in urine by 7 days. The body contained 79% of the remaining radioactivity. The residual radioactivity is associated with prolonged paraquat excretion and, perhaps, progressive lung disease.

Animals↗
PubMed1990

Pharmacokinetics and biliary concentrations of fleroxacin in cholecystectomized patients.

Patients with biliary tract infections received 800 mg of fleroxacin orally once daily on five consecutive days; cholecystectomy was on day 3. Starting on the day when dose 5 was administered, serial blood and T-drain bile samples were taken for 72 h and urine was collected for 96 h. The mean (+/- the standard deviation) peak concentration in plasma was 8.2 +/- 4.0 mg/liter at 8.3 h. The harmonic mean elimination half-life was 10.5 h, which is comparable to that reported for healthy volunteers. This increase resulted from reduced renal clearance (mean [+/- standard deviation], 38 +/- 22 ml/min), as the volume of distribution in the patients (1.4 +/- 0.7 liter/kg) did not differ from that reported for healthy subjects. Maximum concentrations in T-drain bile were high (median, 22.1 mg/liter) and exceeded those measured in plasma by a factor of 2 to 3; the individual ratios of the area under the curve for bile divided by that for plasma ranged from 1.3 to 9.9. As observed in healthy volunteers, the major pathway for elimination of fleroxacin was via the kidneys. The fraction of dose 5 eliminated in the 0- to 24-h urine was reduced, however, and the fraction of the dose in the urine as the N-demethyl and N-oxide metabolites was elevated. At the dose regimen used in this study, the MICs for most pathogens that cause biliary tract infections were surpassed in plasma and bile for more than 24 h.

Adolescent↗
PubMed1990

Pharmacokinetics of intravenous cefetamet and oral cefetamet pivoxil in patients with hepatic cirrhosis.

The pharmacokinetics of orally administered cefetamet pivoxil and intravenously administered cefetamet were studied in 12 healthy subjects and 12 patients with hepatic cirrhosis without ascites. Cirrhosis had no detectable effect on the pharmacokinetics of cefetamet and on the bioavailability of cefetamet pivoxil. After intravenous cefetamet in control versus cirrhotic subjects, respectively, the following mean +/- standard deviation values were observed: total body clearance, 128 +/- 10.2 versus 123 +/- 28.8 ml/min; steady-state volume of distribution, 23.2 +/- 2.2 versus 22.7 +/- 4.6 liters; half-life, 2.42 +/- 0.21 versus 2.35 +/- 0.41 h. Renal and nonrenal clearances of cefetamet were similar in both groups, as were the mean residence times and areas under the plasma concentration-time curve. For oral cefetamet pivoxil, no differences were detected in the mean values of the percentage of dose absorbed: 44.6 +/- 9.1 versus 50.1 +/- 12.9. The rate of appearance of cefetamet in the plasma also was not affected by cirrhosis: similar mean values were found for the mean residence time and the maximum concentration in plasma and its time of occurrence.

Administration, Oral↗
PubMed1989

Presystemic branchial metabolism limits di-2-ethylhexyl phthalate accumulation in fish.

Despite the high lipophilicity of di-2-ethylhexyl phthalate (DEHP), fish do not extensively accumulate this ubiquitous environmental contaminant. Experiments with rainbow trout (Salmo gairdneri) fitted with an indwelling cannula showed that the majority of [14C]DEHP did not reach the systemic circulation of the fish, but was present in the exposure water as metabolites. Pharmacokinetic analysis, using a compartmental model that included the gill as a separate metabolic compartment, indicated that DEHP was extensively metabolized as it diffused from water to blood. Isolated perfused gill arches of trout metabolized DEHP in the exposure bath to monoethylhexyl phthalate, demonstrating the ability of the gill to prevent DEHP entry into the fish. The relationship between metabolic clearance and tissue perfusion further suggests that metabolism in the gill can play an important role in determining the accumulation and toxicity of organic chemical pollutants in fish.

Animals↗
PubMed1989

Pharmacokinetic parameters for interspecies scaling using allometric techniques.

Pharmacokinetic models characterize the kinetic behavior of natural and synthetic substances in animals and man. While the same model structure can generally be used for a particular substance in a variety of species, the values of the model parameters are generally species dependent. Two approaches, allometric and physiologic, may be used to adjust or scale the values of model parameters determined for a substance in one species to predict its pharmacokinetic behavior in other species. In this paper, the allometric approach is applied to pharmacokinetic parameters determined by using compartmental models or "model-independent" methods. Model parameters (Pi) such as mean systemic clearance and steady-state apparent volume of distribution are of interest. Parameter values are determined in several species that vary significantly in body weight (BW). Values of the parameters frequently follow the power function of body weight: Pi = a(BW)b. Interspecies scaling is accomplished in that values of Pi for other species are then estimated from the body weights of those species.

Animals↗
PubMed1989

Intestinal absorption kinetics using a laminar flow model.

The drug concentration profile at non-steady state in the intestine was simulated using a laminar flow model. The transport equation with cylindrical coordinates was solved by a finite difference method to stimulate the concentration profile in the tube and the exit cup-mixing concentration. A drug with a various wall permeability coefficient (Pw = zero or 10(-5) to 10(-3) cm/s) and diffusion constant (D = 10(-6) to 10(-4) cm2/s) was assumed to be introduced into the tube in a pulse form. The spatial intervals of the grid and the time step were varied to yield the optimum condition for calculation. The concentration profile in the tube as the time elapsing and the exit cup-mixing concentration versus time profile were shown graphically. Pw and D influenced the concentration profiles. This suggests the possibility of the estimation of Pw and D by determining the exit cup-mixing concentration after a pulse input to a perfused intestine under a laminar flow condition.

Intestinal Absorption↗
PubMed1989

Metabolism of pentachlorophenol by fish.

1. Interspecies variability in the metabolism of pentachlorophenol (PCP) was investigated by exposing rainbow trout, fathead minnows, sheepshead minnow, firemouth, and goldfish to water-borne 14C-PCP for 64 h. 2. The amounts of metabolites in bile and exposure water were species-dependent; all of the metabolites excreted into the water were sulphate conjugates while bile was enriched in glucuronide conjugates. 3. Biliary excretion accounted for less than 30% of the total PCP metabolites. 4. Biliary metabolites alone were a poor indication of the metabolites produced and of the major routes of elimination.

Animals↗
PubMed1988

Detection of pentachlorophenol and its glucuronide and sulfate conjugates in fish bile and exposure water.

The glucuronide and sulfate conjugates of pentachlorophenol (PCP) that were present in the bile and exposure water of goldfish (Carassius auratus) were used to develop methodology to quantify PCP and its metabolites. Reverse phase HPLC with radioactivity detection separated PCP and its metabolites, and was used to verify a method of quantification that used differential extraction and scintillation counting. Extractions of aqueous phase at pH 2 or 8, with butanol, ethyl acetate, or ether indicated that ether at pH 8 best separated PCP from its metabolites. The sulfate conjugate of PCP was the major metabolite produced when goldfish were exposed to 125 micrograms 14C-PCP/l. It was present primarily in the exposure water, but also appeared in the bile.

Animals↗
PubMed1987

Temperature dependence of di-2-ethylhexyl phthalate (DEHP) pharmacokinetics in rainbow trout.

Rainbow trout (Salmo gairdneri) acclimated at 6, 12, or 18 degrees C received 400 micrograms [14C]DEHP/kg as an intraaortic bolus. DEHP disappeared rapidly from plasma, with an estimated 50% of the dose eliminated after 5 hr. Plasma concentration-time data were analyzed using a three-compartment model and by the statistical moment method; both analyses yielded similar parameter estimates. The apparent steady-state volume of distribution (Vss) and the apparent volume of the deep peripheral compartment (V3) increased exponentially with increasing temperature (log V proportional to temperature) while the volumes of the central (V1) and shallow peripheral (V2) compartments were not systematically affected. The total body clearance of DEHP increased linearly with increasing temperature, while the capacity to hold DEHP increased more rapidly, resulting in the biological persistence and potential for bioaccumulation of DEHP to increase with increased temperature. Both the terminal elimination half-life and the mean residence time increased exponentially with increasing temperature; the half-life increased from 79.5 to 130 hr between 6 and 18 degrees C. Simulations with the model indicated that the distribution of DEHP was temperature sensitive; this finding may have important implications for the temperature sensitivity of DEHP toxicity or carcinogenicity.

Animals↗
PubMed1986

Biliary excretion and pharmacokinetics of ceftriaxone after cholecystectomy.

Three groups of patients with biliary tract disease treated by cholecystectomy were given ceftriaxone. In Group 1 single doses of 150 mg and 1500 mg were given on Days 1 and 5 after cholecystectomy. In Group 2 2 g was given daily for 6 days and the cholecystectomy was on Day 2. Patients in Group 3 received 2 g every 12 h for 3 to 5 doses before cholecystectomy. Plasma samples, urine and T-drain bile were collected at various times from Groups 1 and 2 patients. Gallbladder bile and plasma were collected from Group 3 patients at the time of cholecystectomy. The mean (+/- SEM) T-drain bile-to-plasma concentration ratio of ceftriaxone in Groups 1 and 2 was 6.7 +/- 0.92. The mean (+/- SEM) gallbladder bile-to-plasma concentration ratio was 33 +/- 4.2. No clinically significant differences were detected between the kinetics of ceftriaxone in the cholecystectomy patients compared to normal volunteers. The usual dosage of ceftriaxone appeared adequate for prophylaxis or treatment of biliary tract infection by susceptible organisms.

Adult↗
PubMed1985

Single-dose ceftriaxone kinetics in the newborn.

Ceftriaxone kinetics were characterized after a single, 2-minute, intravenous infusion of 50 mg/kg to 20 sick infants 1 to 8 days old who weighed 1.78 to 4.36 kg. Plasma binding parameters could be determined by equilibrium dialysis in 16 of the infants, in whom kinetic parameters for free ceftriaxone in plasma were also determined. Compared with corresponding values in adults, the elimination t1/2 was longer in infants (19 and 8.4 hours) because of reduced total systemic clearance (4.48 and 8.51 ml/min/m2). The apparent steady-state volume of distribution was of the same order in infants and adults (5,130 and 5,350 ml/m2). Both renal and nonrenal clearance of free ceftriaxone were reduced in infants, but these decreases were partially offset by an increased free fraction; plasma binding affinity and capacity constants for infants were about half the adult values. The mean fraction of dose excreted unchanged in urine was estimated at 70% in the neonates and 46% in adults. There were no clinically significant correlations between the kinetic parameters and either age since birth or age since conception. The fraction of free ceftriaxone in plasma inversely correlated with age since conception and was lower in female infants, which decreased the systemic clearance and volume of distribution of total drug in the female infants compared with the male infants. Values for the volume of distribution and clearance parameters were not related to body size (weight or body surface area). From our results, a ceftriaxone dosage of 50 to 100 mg/day is recommended during the first week of life for newborn infants who weigh between 1.8 and 4.4 kg. Impaired renal function may require a reduction in dosage.

Adult↗
PubMed1985

Low-dose ethanol in the treatment of ethylene glycol poisoning.

A pharmacokinetic study was conducted to determine the effectiveness of lower doses of ethanol in the treatment of ethylene glycol (EG) poisoning. Four dogs were maintained at serum ethanol concentrations of 0, 35 and 140 mg/dl prior to EG (i.v., 2 ml/kg) administration. The serum EG concentration-time data showed that the 35 mg/dl ethanol level provided as effective an inhibition of EG metabolism as did the 140 mg/dl level. The average urinary excretion rate of oxalic acid post EG administration was reduced to control levels by ethanol. The 35 mg/dl serum ethanol level reduced the total body clearance of EG from 93.9 to 50.0 ml/h/kg and increased the effective half-life from 5.78 to 11.4 h. Clinical testing was accomplished by giving the dogs 12 ml EG/kg body weight orally. One hour later, the dogs were either not treated or treated with a sodium bicarbonate-ethanol solution to obtain a serum ethanol concentration of 50 mg/dl. The clinical test performed in the ethanol-treated dogs showed little change from normal limits. Urine calcium oxalate crystals were seldom found. The dogs given EG (12 ml/kg) but not treated with ethanol were in a coma at 13 h and showed severe metabolic acidosis, dehydration, mild hepatocellular disease and acute renal damage. Urine calcium oxalate crystals were found in high numbers. The rapid death associated with EG poisoning appeared to be due to metabolic acidosis in combination with dehydration.

Animals↗
PubMed1984

Aging: effects on beta-carboline binding in hippocampal subfields.

The CA1 and CA4/area dentata subfields of the hippocampus in young, mature and old rats were examined for age-related change in propyl beta-carboline-3-carboxylate (PrCC) binding. 3H-PrCC bound with high affinity (Kd = 0.82 nM) to one binding site when ethyl beta-carboline-3-carboxylate was used to delineate specific binding. An age dependent change in the maximum number of 3H-PrCC binding sites in the CA1 and CA4/area dentate subfields of the hippocampus were assessed by using a saturating (6 nM) concentration of 3H-PrCC. Although 3H-PrCC specific binding at a saturating concentration (6 nM) was significantly less in both the CA1 and CA4/area dentata subfields of the senescent rat, the magnitude of the decrease was greater in the CA1 region. In addition, the affinity of the 3H-PrCC binding site in both subfields probably did not vary significantly with age. Therefore, the CA1 and CA4/area dentate of the rat hippocampus may not only lose BZ1 receptors or the BZ1 receptor conformation with age, but the severity of receptor or receptor conformation loss varies with the subfield.

Aging↗