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L Putcha

Publications and source records attributed to L Putcha.

27 records · Page 2Linked to original sources
PubMed1986

Toxicokinetics and bioavailability of oral and intravenous 1,1-dichloroethylene.

Although aliphatic halocarbons have been identified as contaminants of drinking water supplies, little definitive information is available on their gastrointestinal (G.I) absorption and toxicokinetics. Therefore, a study of a representative halocarbon, 1,1-dichloroethylene (1,1-DCE), was undertaken to contrast the kinetics of the chemical following iv injection with that following oral administration. Four dosage-levels of 1,1-DCE (10, 25, 50, and 100 mg/kg BW) in 50% aqueous polyethylene glycol 400 were given iv and po to fasted and nonfasted male Sprague-Dawley rats. Serial blood samples were taken from the tail artery of the lightly etherized animals for up to 490 min after dosing. 1,1-DCE concentrations in the whole blood were determined by gas chromatographic head-space analysis. Evaluation of the iv data revealed that disappearance of 1,1-DCE from the systemic circulation followed a triexponential pattern. Light ether anesthesia did not appear to alter the pharmacokinetics of iv-injected 1,1-DCE. There was no difference between nonfasted and fasted iv rats in biological half-life (t1/2) or in any other pharmacokinetic parameter. Total body clearance, t1/2, apparent volume of distribution and volume of distribution in the central compartment did show increases with increasing dose in these animals. Oral dosing experiments revealed that 1,1-DCE was absorbed very rapidly and completely from the G.I. tract. Peak blood levels were reached 2 to 8 min following oral administration of 1,1-DCE as an aqueous suspension. The t1/2 of 1,1-DCE in orally dosed rats was somewhat longer than in their iv counterparts. The t1/2 values for nonfasted, orally dosed rats were longer than for their fasted counterparts, suggesting delayed absorption due to the presence of food in the G.I. tract. Bioavailability of 1,1-DCE, as determined by comparing areas under blood concentration versus time curves (AUCs), was equivalent in animals given the same dose of 1,1-DCE iv and po. AUCs increased with increasing dose in iv and po groups, but the increases were not proportional to dose.

Administration, Oral↗
PubMed1985

Pharmacokinetics of acetohydroxamic acid in patients with staghorn renal calculi.

Acetohydroxamic acid (AHA), a bacterial urease inhibitor, has been recently approved by the United States Food and Drug Administration as a potential drug for the successful treatment of patients with infection induced staghorn renal calculi. The present study was designed to evaluate the disposition of 14C-AHA following oral administration to patients. The results of the study, while in a limited number of patients, indicate that upon oral administration, AHA is very rapidly absorbed from the gastrointestinal tract. Evaluation of urinary excretion data suggests that patients with compromised renal function have low recoveries of AHA in the urine. These data are supported by a strong linear correlation between creatinine clearance and AHA elimination. Acetamide and CO2 are identified as the two major metabolites of AHA in man. CO2 is eliminated in the breath and accounts for 20-45% of the administered dose, while acetamide is eliminated in the urine and accounts for only 9-14% of the administered dose. The remaining dose is eliminated as intact AHA in the urine (19-48%). Saliva concentrations of total radioactivity depict a strong positive correlation with their respective plasma concentrations. Parameter estimates from 14CO2 concentrations in breath as a function of time data closely correspond to the pharmacokinetic parameters of AHA in patients indicating that CO2 may be a primary metabolite derived directly from AHA rather than a secondary metabolite formed by the metabolism of an intermediate product. Upon multiple dose administration of AHA, there is the potential for significant accumulation of acetamide due to its relatively long half-life.

Acetamides↗
PubMed1983

The uptake and disposition of 1,1-dichloroethylene in rats during inhalation exposure.

The uptake, disposition, and respiratory elimination of 1,1-dichloroethylene (1,1-DCE) during inhalation exposure were evaluated to gain insight into the pharmacodynamics of the halocarbon. Anesthetized male Sprague-Dawley rats inhaled 25, 75, 150, or 300 ppm 1,1-DCE for 3 hr from an aluminized Mylar bag through a miniaturized one-way breathing valve inserted into the trachea. Periodic air samples were taken immediately adjacent to the valve from the separate inhaled air and exhaled breath streams concurrently with blood samples from a cannulated femoral vein and analyzed for 1,1-DCE content by gas chromatography. 1,1-DCE was absorbed very rapidly, in that substantial levels were present in the venous blood at the first sampling time (i.e., 2 min). Percentage systemic uptake decreased over time after initiation of exposure until equilibrium was established. Percentage uptake after reaching equilibrium varied inversely with the exposure concentration. 1,1-DCE venous whole-blood levels in animals exposed to 25, 75, and 150 ppm 1,1-DCE increased rapidly to near steady state within approximately 45 min, as did concentrations of 1,1-DCE in the exhaled breath and alveolar air. Calculation of the amount of 1,1-DCE taken up by the body over the course of the 3-hr exposures revealed that cumulative uptake of the inhaled chemical was statistically linear for the 25-, 75-, and 150-ppm exposures. Accumulation plots for 300-ppm exposed animals, however, were best fitted to a cubic curve form. Although trends toward the establishment of equilibrium were initially seen in the 300-ppm exposed animals, levels of 1,1-DCE in the blood and breath rose progressively during the latter hour of the 3-hr exposure period. Thus, despite increased exhalation of 1,1-DCE, these animals could not prevent systemic accumulation of the chemical.

Animals↗
PubMed1982

A simple method for repetitive blood sampling from rats.

A convenient, reliable method for obtaining serial blood samples from rats is described. A simple cannula device is maintained in the ventral caudal artery of lightly etherized rats. Sequential blood samples of desired volume can be taken as frequently as needed without wastage. The technique is minimally traumatic to the animal and does not require extensive preparatory time. Since airtight blood samples can be taken, the technique can be used for pharmacokinetic studies of volatile compounds.

Animals↗
PubMed1978

Pharmacokinetics of acetohydroxamic acid. Preliminary investigations.

The pharmacokinetics of acetohydroxamic acid (AHA), an agent being evaluated in the treatment of infection-induced urinary stones, have been examined in rats and man. After oral and intravenous administration of AHA to rats the biologic half-life and total body clearance seemed to be dose dependent. Comparison of the oral and intravenous data indicated that less than 100 per cent of an oral dose of AHA reaches the systemic circulation intact and that this percentage is dose related. Studies performed in human subjects indicated that AHA is rapidly absorbed from the gastrointestinal tract and has a biologic half-life of 5 to 10 hr in subjects with normal renal function. The half-life and percent of dose recovered in the urine seem to be dose related and dependent upon renal function.

Administration, Oral↗
PubMed1978

Effect of heptabarbital on bioavailability of bishydroxycoumarin in the rat.

The influence of oral administration of heptabarbital on the gastrointestinal absorption of bishydroxycoumarin (BHC) was investigated in rats. Pretreatment of the animals with 20 mg/kg heptabarbital twice dialy for three days prior to the administration of 50 mg/kg BHC resulted in a 40% decrease from controls in the area under the BHC plasma concentration time curve (AUC). Preliminary studies indicated that a similar decrease in gastrointestinal absorption of BHC could be seen following a single oral dose of heptabarbital administered concomitantly with the anticoagulant.

Administration, Oral↗
PubMed1977

Effect of anti-parkinsonism drugs on gastric emptying and intestinal transit in the rat.

The effect of atropine sulfate, trihexyphenidyl HCl, benztropine mesylate, diphenhydramine HCl and ethopropazine HCl on gastric emptying and intestinal transit of a phenol red solution in the rat was examined. Intraperitoneal administration of 0.3 mg/kg atropine, 1.2 mg/kg benztropine and trihexyphenidyl results in a marked decrease in gastric emptying and intestinal transit rate when compared to controls. Oral administration of these agents produced variable and unpredictable results. Single and multiple oral dose (0.6--3 mg/kg) studies with trihexyphenidyl failed to produce any significant decreases in gastric emptying rates. A single oral dose of benztropine (0.6--3 mg/kg) failed to reduce the gastric emptying rate, but multiple dose studies produced a significant decrease in the gastric emptying rate. Effects on gastric emptying and intestinal transit were seen after single and multiple oral doses of diphenhydramine and ethopropazine.

Administration, Oral↗
PubMedDate not supplied

Disposition of 14C-acetohydroxamic acid and 14C-acetamide in the rat.

Acetohydroxamic acid (AHA) has been identified as a potential agent for the treatment of infection-induced staghorn renal calculi in patients. The pharmacokinetics and disposition of 14C-acetamide have been evaluated in rats following iv and oral administration. The results of these experiments suggest that, following oral administration to rats, AHA is absorbed very rapidly from the gastrointestinal tract and is metabolized to acetamide and CO2. Approximately 50-56% of the iv dose and 40-49% of the oral dose of 14C-AHA is excreted in the urine, suggesting a significant nonrenal elimination pathway for AHA and metabolite(s). This view is supported by the fact that a significant portion of the administered radioactivity (6-10%) is eliminated by the breath as 14CO2. Administration of 14C-acetamide to rats revealed that the compound is predominantly eliminated via the renal route, accounting for 68% of the administered radioactive dose. However, approximately 30% of the dose in the case of both AHA and acetamide could not be recovered, either in the urine or in the breath, during the 72-hr period of the experiment. This suggests that acetamide, either by direct administration or derived as a metabolite of AHA in the rat, may undergo further metabolism to get incorporated into the acetate pool. This would result in very slow elimination of the remaining activity as 14CO2 or as another unknown metabolite.

Acetamides↗