PubMed Health⌕ Search

Biomedical subjects

W R Ravis

Publications and source records attributed to W R Ravis.

72 records · Page 4Linked to original sources
PubMed1985

Pharmacokinetic calculator program for generation of initial parameter estimates from a three-compartment infusion model.

A polyexponential curve-stripping program, KIN, is described for use on the HP-41CV programmable calculator. The program may be used in the analysis of plasma-concentration-time curves for a three-compartment intravenous bolus or infusion model with linear elimination processes. The coefficients and hybrid rate constants of the exponential function are then used to compute pharmacokinetic parameters (volume of the central compartment, intercompartmental rate transfer constants), which may be used as initial estimates of model parameters in non-linear regression curve-fitting procedures.

Computers↗
PubMed1985

DATALIN--an interactive data entry program for use with NONLIN.

A package of FORTRAN programs for data entry into NONLIN (version II) is described which may be used in the analysis of plasma-concentration time curves after single or multiple doses for fourteen pharmacokinetic models described in terms of the model's microconstants (volume of compartments, rate constants). In all cases, infusion rates must be zero-order and absorption rates first-order. The program contains an edit subroutine allowing for changes in initial parameter estimates and their lower and upper limits, weighting factors, number of iterations in the NONLIN analysis, and plot option. Individual X and Y values may be changed and listed and X-Y data pairs may be inserted or deleted. Factors pertaining to each of the data entries in relation to NONLIN are discussed.

Animals↗
PubMed1985

Pharmacokinetics of prednisolone sodium succinate and its metabolites in normovolemic and hypovolemic dogs.

Tritium-labeled prednisolone sodium succinate was administered IV to 4 healthy, awake, nonsplenectomized dogs. The concentration of prednisolone and its metabolites in the plasma were measured for 10 hours. Forty-one percent of the blood volume of these dogs was removed, and plasma prednisolone was measured again. The data before and after hemorrhage were fitted to a 2-compartment open model. From plasma profiles, a rapid distributional phase, followed by a slower phase, was observed in control and shock groups. Volume of the central compartment of prednisolone before and after hemorrhage was 165 ml/kg of body weight and 110 ml/kg, respectively; and the difference was significant (P less than 0.05). The rate of total body clearance of prednisolone before and after hemorrhage was 3.96 ml/min/kg and 2.53 ml/min/kg, respectively; the difference was significant. The mean plasma half-lives for prednisolone sodium succinate and its metabolites, before and after hemorrhage, were 166 and 197 minutes, respectively; the difference was not significant. The mean half-life data indicated that prednisolone sodium succinate may be repeated in a patient 2.5 to 3 hours after onset of treatment if signs of hypovolemic shock reappear.

Animals↗
PubMed1985

Endometrial and serum gentamicin concentrations in pony mares given repeated intrauterine infusions.

Endometrial tissue and blood serum gentamicin (GT) concentrations were determined in 6 ovariectomized pony mares given intrauterine infusions (50 ml of a 5% commercial aqueous solution of GT) each day for 5 consecutive days. The mares were subjected to the following 3 treatments: (1) GT infusion only (trial A, control); (2) progesterone plus GT (trial B, P + G); and (3) estradiol plus GT (trial C, E + G). Endometrial tissue concentrations of GT (micrograms/g) at 24 and 120 hours were significantly higher (P less than 0.05) in trials B (65.54 +/- 15.57 and 100.33 +/- 19.27) and C (73.33 +/- 22.53 and 74.09 +/- 8.60) than in trial A (4.23 +/- 0.70). Endometrial concentration for trial A at 120 hours was also significantly higher than trial A at 24 hours. There was no significant difference (P greater than 0.05) in endometrial concentrations among trials A, B, and C at 120 hours. Serum GT concentrations were significantly lower than endometrial tissue concentrations. The highest serum concentrations of GT found in every trial occurred at 6 hours after each intrauterine infusion of GT. The highest overall serum concentration of GT (micrograms/ml) determined occurred in trial B (8.30 +/- 1.28) at 78 hours. There was no significant difference in serum concentrations of GT between days of treatment, except for trial A at 78 and 102 hours, respectively. Serum concentrations of GT were significantly higher (P less than 0.05) than trial A at 30, 54, 78, and 102 hours in trial B, and at 78 and 102 hours in trial C. There was no significant difference in serum concentrations of GT between trials B and C.

Animals↗
PubMed1985

Pharmacokinetics of gentamicin at steady-state in ponies: serum, urine, and endometrial concentrations.

Gentamicin (GT) was administered IM to 6 healthy mature mare ponies at a dosage of 5 mg/kg of body weight every 8 hours for 7 consecutive days (total, 21 doses). Two venous blood samples were collected before (trough) and at 1 hour (peak) after the 5th, 10th, 14th, and 19th doses. An endometrial biopsy was done of each mare on days 4 and 7. On the 7th day, just before the 21st administration of GT, base-line blood samples were collected, and 22 blood samples were collected over a period of 48 hours after GT was given. The mares were catheterized on the 7th day, and urine was collected for 24 hours. Serum, urine, and endometrial GT concentrations were determined by a radioimmunoassay technique (sensitivity of 0.3 micrograms/ml of serum). Serum GT concentration data obtained from the terminal phase were best fitted by a 1-compartment open model with a biological half-life of 2.13 +/- 0.43 hours. Total body clearance and renal clearance were 1.69 +/- 0.41 and 1.40 +/- 0.26 ml/min/kg, respectively. Mean endometrial concentrations on day 4 and day 7 were 5.02 +/- 3.3 and 12.75 +/- 1.6 micrograms/g. To achieve mean serum GT concentrations (micrograms/ml) at steady state of 6.47 +/- 1.51, a maximum steady-state concentration of 12.74 +/- 1.60, and a minimum steady-state concentration of 1.43 +/- 0.57, a dosage of 5 mg/kg every 8 hours is recommended. Serum urea nitrogen, serum creatinine, and the fractional clearance of sodium sulfanilate were determined before and after GT treatment. Renal function remained within the base-line range during 7 days of GT administration.

Animals↗
PubMed1985

Combined pharmacokinetics of gentamicin in pony mares after a single intravenous and intramuscular administration.

Healthy mature pony mares (n = 6) were given a single dose of gentamicin (5 mg/kg of body weight) IV or IM 8 days apart. Venous blood samples were collected at 0, 5, 10, 20, 30, and 45 minutes and at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, 24, 30, 36, 40, and 48 hours after IV injection of gentamicin, and at 10, 20, 30, and 45 minutes and at 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, 12, 18, 24, and 30 hours after IM injection of gentamicin. Gentamicin serum concentration was determined by a liquid-phase radioimmunoassay. The combined data of IV and IM treatments were analyzed by a nonlinear least-square regression analysis program. The kinetic data were best fitted by a 2-compartment open model, as indicated by residual trends and improvements in the correlation of determination. The distribution phase half-life was 0.12 +/- 0.02 hour and postdistribution phase half-life was 1.82 +/- 0.22 hour. The volume of the central compartment was 115.8 +/- 6.0 ml/kg, volume of distribution at steady state was 188 +/- 9.9 ml/kg, and the total body clearance was 1.27 +/- 0.18 ml/min/kg. Intramuscular absorption was rapid with a half-life for absorption of 0.64 +/- 0.14 hour. The extent of absorption was 0.87 +/- 0.14. Kinetic calculations predicted that IM injections of 5 mg of gentamicin/kg every 8 hours would provide average steady-state serum concentrations of 7.0 micrograms/ml, with maximum and minimum steady-state concentrations of 16.8 and 1.1 micrograms/ml, respectively.

Animals↗
PubMed1985

Binding of warfarin by human albumin in the presence of a perfluorochemical blood substitute.

The effect of a perfluorochemical blood substitute on ligand binding by human albumin was examined using warfarin as a model drug. Binding of warfarin by four per cent human albumin solutions diluted with either buffer or blood substitute, and by blood substitute diluted with buffer was examined. Solutions containing 2 or 10 micrograms/ml warfarin were quantitated by liquid scintillation counting using 14C-warfarin. The per cent warfarin free at room temperature was determined by centrifugation followed by supernatant ultrafiltration. Warfarin was weakly bound by the blood substitute and the overall effect of albumin dilution with the blood substitute was an increase in per cent warfarin free. Blood substitute binding of warfarin may explain the decrease of per cent warfarin free observed when albumin solutions were diluted to 50 and 75% v/v with blood substitute rather than buffer. However, the per cent warfarin free increased when albumin solutions were diluted to 25% v/v with blood substitute rather than buffer. The fraction free increased by 39.0% and 30.4% at total warfarin concentrations of 2 and 10 micrograms/ml, respectively. This relative increase in per cent warfarin free may be the result of a direct and/or indirect displacement of albumin bound warfarin by a component(s) of the blood substitute.

Blood Substitutes↗
PubMed1984

Intestinal absorption and metabolism of 6-mercaptopurine in the rat small intestine.

The intestinal absorption of 6-mercaptopurine was examined in the rat by in vitro and in situ techniques for the purpose of establishing absorption characteristics which might explain the poor systemic oral availability of this drug. Experiments were designed to evaluate the significance of intestinal metabolism and active secretion processes. Since mucosal/serosal drug concentration gradients across in vitro segments were not significantly different (P greater than 0.05) for everted and noneverted preparations, with values of 1.21 +/- 0.27 and 0.91 +/- 0.12, respectively, it was concluded that active secretion or absorption mechanisms were absent. Varying the concentration of 6-mercaptopurine from 0.24 to 5.88 mM demonstrated saturability of the biotransformation of 6-mercaptopurine to 6-thiouric acid with a maximum rate of 1.6 X 10(-5) mmoles per min g for jejunal portions. Distal segments displayed 85% higher rates of biotransformation at concentrations of 1.47 mM. Inclusion of allpurinol (2 mM) completely inhibited biotransformation. With in situ loops perfused with 1.47 mM drug, collection of mesentery blood showed that absorption rates of 6-thiouric acid were 0.67 that of the parent drug.

Animals↗
PubMed1984

Anticonvulsant activity of some 4-aminobenzamides.

A series of 4- aminobenzamides of some simple primary and secondary amines were prepared and evaluated for anticonvulsant effects. The compounds were tested in mice against seizures induced by electroshock and pentylenetetrazole ( metrazole ) and in the rotorod assay for neurologic deficit. For those N-alkyl amides tested, 4-amino-N- amylbenzamide (6) was the most potent against maximal electroshock seizures (MES): ED50 = 42.98 mg/kg; however, the N- cyclohexylbenzamide (8) showed the greatest protective index (PI = TD50/ED50), 2.8. The introduction of a second aromatic ring produced more potent compounds, with d,l-4-amino-N-(alpha-methylbenzyl)-benzamide (12) showing the highest level of activity. This compound has an anti-MES ED50 of 18.02 mg/kg in mice when administered intraperitoneally (ip) and a TD50 of 170.78 mg/kg (PI = 9.5) in the same species. These data compare quite favorably with those for phenobarbital and phenytoin in the same assays.

Animals↗
PubMed1983

Cortisol (hydrocortisone) disappearance rate and pathophysiologic changes after bilateral adrenalectomy in equids.

Six ponies and 1 horse were bilaterally adrenalectomized (BADX). The survival time of 2 of the 7 animals after BADX was 24 and 72 hours without supplemental corticosteroids. The cause of death was not related to the surgical technique. The biological half-life of cortisol (hydrocortisone) was estimated to be 2.1 +/- 0.6 hours. The disappearance of cortisol in the horse was found to be biphasic, composed of redistribution and elimination phases. Pathophysiologic changes (ie, increased serum sodium and chloride, increased PCV, and decreased serum potassium) similar to those seen in other species after BADX were found. Clearance of electrolytes was calculated, using the creatinine clearance method. These values were inversely correlated with the changes seen in serum electrolytes.

Adrenalectomy↗
PubMed1981

Dissolution, stability, and absorption characteristics of dicumarol in polyethylene glycol 4000 solid dispersions.

The dissolution characteristics of dicumarol were markedly enhanced by preparing dispersions of drug in polyethylene glycol 4000. Solid dispersions of varying weight fractions were formed by a melt method without measurable drug degradation or evaporation. There were no significant differences in dissolution rates among weight fractions, with dynamic solubilities being approximately 2.5 times greater than dicumarol's equilibrium solubility. No indications of drug polymer complexation were noted from equilibrium or in situ absorption experiments. Incorporation of solid dispersions into direct compression tablets provided dosage forms with fast-release properties relative to test tablets of physical mixtures and a commercially available product. Percentages dissolved in 30 min were 370% greater for 1:3 and 1:5 (w/w) solid dispersion tablets compared to a commercial tablet at 37 degrees with a pH 7.5 dissolution buffer. X-ray diffraction of test powder revealed that the crystalline nature of the drug had altered during fusion preparation. Dissolution traits and drug stability for solid dispersions were maintained over 1 year of storage.

Absorption↗
PubMed1981

Pharmacokinetics of a single, orally administered dose of digoxin in horses.

Digoxin (elixir, 0.022 mg/kg) was administered via stomach tube to healthy horses of mixed breeding and sexes. Serum digoxin concentrations reached a peak (2.21 +/- 0.6 ng/ml) at approximately 1 hour after dosing and had a half-life of 28.8 +/- 10.7 hours. Digoxin kinetics followed a triexponential curve, indicating that at least a 2 compartmental model is required to characterize the serum concentration-time curve after this route of administration. It was calculated that to achieve average serum concentrations of 1.1 ng/ml, an oral dose of 17.4 microgram of digoxin elixir/kg/day and an IV dose of 6.1 microgram of parenteral preparation/kg/day would be required. There was no significant (P greater than 0.05) alteration in base-line serum calcium, potassium, and sodium concentrations and heart rate, P-R interval, and mean arterial blood pressure.

Administration, Oral↗
PubMed1980

Pharmacokinetics of gentamicin in the horse.

The pharmacokinetics of gentamicin were studied in six healthy mature horses of mixed breeding and of both sexes. A parenteral preparation of gentamicin sulfate (5% aqueous solution) was administered rapidly (IV) at the dosage level of 5 mg/kg of body weight. Venous blood samples were taken at 0 (base line), 0.083, 0.25, 0.5, 0.75, 1, 2, 4, 8, 12, 24, 36, 48, 72, 96, and 120 hours after gentamicin administration. Serum gentamicin was measured by a radioimmunoassay technique. The gentamicin concentration data was fitted to a one- and two-compartment open model with first-order elimination from the central compartment with the aid of nonlinear least squares program. The data were found to be best described by the two-compartment model with r2 = 0.997. Half-life, as determined from the terminal phase was 2.54 +/- 0.33 hours. Calculation of the total body clearance provided a mean of 1.16 +/- 0.11 ml/minute/kg of body weight (1.04 to 1.31 ml/minute/kg, range); the volume of distribution calculated from the area under the curve was determined separately for each animal and had a mean value of 0.254 +/- 0.036 L/kg. The initial exponential decline (alpha) in gentamicin serum concentration had an average value of 3.75 +/- 1.86 hours-1, whereas the terminal values were described by beta = 0.275 +/- 0.036 hours-1. Other pharmacokinetic values determined also are presented.

Animals↗
PubMed1979

Effect of enzyme-inducing and enzyme-inhibiting agents on drug absorption. II. Influence in proadifen on 3-O-methylglucose transport in rats.

Studies utilizing the in vitro everted rat jejunum were performed to investigate the effects of proadifen pretreatment and fasting on active and passive intestinal transfer of 3-O-methylglucose. Animals were pretreated 24 hr prior to the experiments with 100 mg of proadifen/kg ip. With mucosal concentrations of 0.1 mM 3-O-methylglucose and 14C-3-O-methylglucose, transfer to the sugar-free serosal buffer after pretreatment with proadifen was 50% greater than controls after a 24-hr fast and 120% greater than controls after a 48-hr fast. Everted intestinal segments obtained from unfasted control animals showed diminished ability to transfer the sugar derivative, with transfer rates approximately 50% less than those of segments obtained from 24-hr fasted control animals. Wet and dry tissue weights for 24- and 48 hr-fasted groups increased following proadifen pretreatment. The results suggest that proadifen enhances 3-O-methylglucose transport across the rat jejunum and also increases intestinal tissue weight.

Animals↗
PubMed1978

Effect of enzyme-inducing and enzyme-inhibiting agents on drug absorption I: 3-O-methylglucose transport in rats.

The influence of preadministration of phenobarbital, benzo[alpha]pyrene, and proadifen hydrochloride on 3-O-methylglucose transfer across the everted rat small intestine was examined. The active and passive components of the sugar transport mechanism were evaluated using phlorizin, a potent inhibitor of active transport of sugars. Pretreatment of the animals with phenobarbital did not alter 3-O-methylglucose transfer characteristics. Pretreatment with intraperitoneally administered benzo[alpha]pyrene increased mucosal to serosal transfer of the sugar low (0.1 mM) sugar concentrations. Enhancement of the active transfer of 3-O-methylglucose by pretreatment with proadifen hydrochloride was noted at low sugar concentrations. The passive transfer of the sugar was reduced after pretreatment with proadifen hydrochloride.

Animals↗
PubMedDate not supplied

Pharmacokinetics of insulin following intravenous and subcutaneous administration in canines.

Studies were conducted to examine the absorption and disposition kinetics of insulin in dogs following intravenous (IV) and subcutaneous (SC) administration of commercial preparations. After IV and SC dosing, the plasma levels were described by models which considered basal insulin level contributions. Intersubject variation in the disposition kinetics was small with half-lives of 0.52 +/- 0.05 h and total body clearances of 16.21 +/- 2.08 ml min-1 kg-1. Calculated insulin plasma secretion rates in the canines were 14.4 +/- 3.3 mUh-1 kg-1. Following SC injection of regular insulin, the rate and extent of absorption were noted to be quite variable. The absorption process appeared first-order with half-life values of 2.3 +/- 1.3 h and extents of absorption of 78 +/- 15 per cent with a range of 55-101 per cent. Insulin absorption from SC NPH preparations was evaluated as being composed of two zero-order release phases, a rapid and a slow release phase. With a dose of 1.65 U kg-1, the rapid release phase had an average duration of 1.5 h and a rate of 580 +/- 269 mUh-1 (4.2 per cent of dose) while the slow phase had a zero-order rate of 237 +/- 92 mU h-1 which continued beyond 12 h. The extent of absorption from the NPH preparation was 23.6 +/- 5.1 per cent and was significantly lower than that for the regular injection.

Child↗
PubMedDate not supplied

Serum concentrations of digoxin entrapped in liposomes after intravenous administration in dogs.

1. Digoxin was associated into phosphotidylcholine liposomes at concentrations of 28-33 mol% in Hank's Buffer, pH 7.4 at 28 degrees C. 2. Digoxin-liposomes (digoxin concentration 0.022 mg/kg per dog per day) administered intravenously in five adult male dogs attained therapeutic serum concentrations (0.7-3.0 ng/ml) beginning with day 1 of administration. 3. Digoxin serum concentrations obtained by intravenous digoxin-liposomes compared favorably with normal oral digoxin administration (0.022 mg/kg per dog per day) in all 5 dogs monitoring serum digoxin levels for 7 days showed no significant (P < 0.05) differences in mean serum digoxin concentrations +/- s.e.m. on 6 of 7 days of treatments.

Administration, Oral↗