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Biomedical subjects

V K Batra

Publications and source records attributed to V K Batra.

17 recordsLinked to original sources
PubMed1994

Angiotensin II elevates cytosolic free calcium in human lung adenocarcinoma cells via activation of AT1 receptors.

Angiotensin II (Ang II), bradykinin (BK), and endothelin-1 (ET-1) evoked alterations in cytosolic free calcium, [Ca2+]i, levels were determined using fura-2 fluorescence methodology in a human lung adenocarcinoma cell line (A549), a non-neoplastic lung cell line and a small cell lung carcinoma cell (SCLC) line. Ang II and BK evoked a rapid, concentration-dependent transient increase in [Ca2+]i in A549 cells. The peak [Ca2+]i increases attained with Ang II (1 microM) and BK (1 microM) were 3- and 4-fold higher, respectively (P < 0.01) than the basal [Ca2+]i values. This effect of Ang II was completely abolished by inclusion of losartan (DuP 753), an AT1 subtype selective antagonist. Removal of extracellular Ca2+ from the incubation medium led to significant diminution of the peak [Ca2+]i response to Ang II but not to BK. In contrast to Ang II and BK, ET-1 failed to evoke an increase in [Ca2+]i levels in A549 cells. Neither Ang II nor ET-1 evoked any appreciable increase in [Ca2+]i levels of non-neoplastic lung cell and SCLC cell lines. These data confirm that the human non-small cell lung cancer cells (A549) selectively express AT1 subtype receptors for Ang II that are functionally coupled to Ca2+ mobilization from both extra and intracellular sources.

Adenocarcinoma↗
PubMed1993

ETB receptors on aortic smooth muscle cells of spontaneously hypertensive rats.

The effect of the agonist sarafotoxin 6c (S6c), selective for endothelin (ET) receptor subtype B (ETB), on cytosolic free Ca2+ concentrations ([Ca2+]i) was determined by fura-2 methodology using aortic smooth muscle cells (ASMC) isolated from spontaneously hypertensive rats (SHR) and two normotensive strains, Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats. The basal [Ca2+]i was significantly higher in the ASMC of SHR (139 +/- 8 nM) than WKY (107 +/- 7 nM) and SD (102 +/- 4 nM) rats. S6c produced concentration-dependent elevations in [Ca2+]i in the ASMC of WKY and SHR, whereas it did not evoke significant increases in the [Ca2+]i levels in the ASMC of SD rats. The peak [Ca2+]i levels observed with maximal concentrations of S6c (500 nM) was higher (P < 0.01) in the SHR (346 +/- 36 nM) than the WKY group (148 +/- 19 nM). The natural nonselective agonist, ET-1, evoked maximal [Ca2+]i in the ASMC of SHR, WKY, and SD rats of 635 +/- 43, 304 +/- 19, and 289 +/- 24 nM, respectively. Depletion of extracellular Ca2+ concentration led to the reduction of the peak [Ca2+]i response to ET-1 by 60 and 40% in the WKY and SHR cells, respectively, whereas the response to S6c remained unaffected. The ETA-selective antagonist, BQ-123 (1 microM), did not affect the [Ca2+]i response to S6c, whereas it attenuated the response to ET-1 by 90 and 70% in the WKY and SHR cells, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Pneumadin: a new lung peptide which triggers antidiuresis.

Normal mammalian lungs, including human fetal lungs, contain significant amounts of a decapeptide which releases arginine-vasopressin from the neurophypophysis and therefore has antidiuretic activity. The rat peptide is: Tyr-Gly-Glu-Pro-Lys-Leu-Asp-Ala-Gly-Val-NH2. The peptide from human fetal lungs has Ala instead of Tyr. It may be a normal regulatory substance and its role in the pathogenesis of the syndrome of inappropriate antidiuresis associated with lung diseases merits investigation. In view of its source and action, the antidiuretic lung peptide may be called Pneumadin.

Amino Acid Sequence↗
PubMed1987

Dose-dependent pharmacokinetics of a new oral cephalosporin, cefixime, in the dog.

Cefixime (CL 284,635; FK 027) is a new third-generation oral cephalosporin. To study dose-dependent pharmacokinetics of cefixime in dogs, two balanced four-way crossover studies were conducted. In the first study, oral doses of 50, 100, and 200 mg/kg and an intravenous dose of 50 mg/kg cefixime were administered. In the second study, oral doses of 6.25, 12.5, and 25 mg/kg and an intravenous dose of 12.5 mg/kg cefixime were administered to the same dogs. A period of 1 month separated the two studies. When the two intravenous doses were compared (i.e., 12.5 and 50 mg/kg), a twofold increase in clearance and volume of distribution was observed after the higher dose. The oral systemic bioavailability in the dose range 6.25-50 mg/kg was 55%. It decreased to 44% at 100 mg/kg and 27% at 200 mg/kg. The average peak serum concentrations ranged from 15.8 micrograms/ml at 6.25 mg/kg to 119 micrograms/ml at 200 mg/kg. Within this concentration range, the fraction of free drug in serum (unbound to proteins) increased from 7 to 25%. This concentration-dependent protein binding was primarily responsible for changes in total clearance, volume of distribution, and bioavailability of the drug in dogs.

Administration, Oral↗
PubMed1986

Pharmacokinetics of mitoxantrone in man and laboratory animals.

Mitoxantrone (NOVANTRONE), an anthracenedione, is a novel anticancer agent with a wide spectrum of antitumor activity. Its anticancer activity is comparable to that of doxorubicin but with apparently significantly reduced cardiotoxicity. The recommended dosage regimen for the treatment of breast carcinoma is 12-14 mg/m2 given intravenously once every 21 days. Intravenously administered mitoxantrone disappears from the plasma of man and laboratory animals with multiexponential kinetics and with the terminal half-life ranging from 38 h to several days. It is rapidly cleared from the plasma by extensive sequestration into the tissues of the rat, dog, monkey, and man. However, redistribution back into the plasma and elimination from the body are slow processes. In both animals and man it is metabolized to the mono- and dicarboxylic acid derivatives, as well as glucuronide conjugates of these acids. Following intravenous administration, it is unchanged mitoxantrone that binds to most tissues. Rats, dogs, monkeys, and man, all eliminate mitoxantrone and its metabolites slowly by both renal and biliary excretion, with the biliary route predominating.

Animals↗
PubMed1985

Capillary gas chromatographic-mass spectrometric analysis of 15-deoxy-16-hydroxy-16-vinylprostaglandin E2.

A new topically active antihypertensive agent, the methyl ester of 15-deoxy-16-hydroxy-16-vinylprostaglandin E2 (1), rapidly hydrolyzes in blood to the carboxylic acid 2, which also has antihypertensive activity. A capillary gas chromatographic-mass spectrometric method is described for measuring 2 in human plasma or serum at expected experimental blood levels of 75-1500 pg/mL. The assay is based on selected-ion monitoring of the carboxylate anion formed from negative ion chemical ionization of the trimethylsilylpentafluorobenzyl ester of 2, using a trideuterated analogue of 2 as internal standard. The method has been used to analyze samples from subjects following topical application of 1-2 mg of 1. Sample preparation included isolation from 1 mL of plasma or serum and purification of the ester derivative with C18 cartridges, followed by a two-step trimethylsilylation.

Antihypertensive Agents↗
PubMed1983

Pharmacokinetics of piperacillin and gentamicin following intravenous administration to dogs.

Piperacillin sodium was administered intravenously to dogs, alone or in combination with gentamicin, twice a day (approximately 5 hr apart) for 36-37 days. The pharmacokinetics of neither drug changed in the presence of the other; however, the percentage of the gentamicin dose recovered in the urine decreased significantly when coadministered with piperacillin. The data demonstrate that interaction between the two drugs in urine is feasible.

Animals↗
PubMed1980

Intrathecal human tetanus immunoglobulin in early tetanus.

97 patients with symptoms of early tetanus at the time of admission to hospital were treated with sedation, antibiotics, and human tetanus immune globulin (TIG). After intrathecal TIG 250 IU 3 patients out of 49 got worse but only 1 died while in a closely similar group of 48 patients in whom TIG was administered intramuscularly in dose of 1000 IU, the clinical features of the disease became severer in 15 (31%) and 10 (21%) died. The intrathecal use of TIG was devoid of side effects.

Adolescent↗
PubMed1979

Piperacillin kinetics.

Piperacillin was administered to normal, healthy volunteers by an intravenous infusion over 30 min at dosage regimens of 12 gm daily (4 gm every 8 hr) and 24 gm daily (6 gm every 6 hr) for 5 consecutive days. Mean peak serum level after 12 gm daily was 244 +/- 24 (SE) microgram/ml and after 24 gm daily, 353 +/- 7 microgram/ml. After infusion the serum level declined monoexponentially in most subjects. On the 12-gm daily dosage mean values were 60 min for half-life (t1/2), 16 1 for volume of distribution, 188 ml/min for body clearance, and 139 ml/min for renal clearance. The same values on day 4 were 47 min, 12 1, 181 ml/min, and 125 ml/min; the volume of distribution was lower than on day 1. On the 24-gm daily dosage regimen, t1/2 was 60 min; volume of distribution, 16 1; body clearance, 183 ml/min; and renal clearance, 101 ml/min on day 1 compared to 68 min, 15 1, 148 ml/min, and 71 ml/min on day 4, the last 2 being significantly lower than on day 1. High renal clearance values were observed at low serum concentrations and vice versa, suggesting saturation of the tubular secretion process at high piperacillin concentrations in serum.

Adolescent↗
PubMed1979

Plasma naltrexone kinetics after intravenous bolus administration in dogs and monkeys.

This investigation generated data characterize a specific electron-capture GLC assay reported previously for naltrexone and applied the method to a determination of naltrexone pharmacokinetics. Extraction efficiencies are reported for the assay, and mass spectral evidence indicates that naltrexone forms a triester when derivatized for electron-capture GLC with pentafluoropropionic anhydride and a base catalyst. Plasma level-time data for intravenous naltrexone at two dose levels in monkeys yielded no evidence of dose-dependent kinetics. A two-compartment open pharmacokinetic model was fitted to plasma level-time data for naltrexone in two dogs and yielded a total body clearance of 51-55 ml/min/kg. Urine collected for 0-24 hr contained 36% of the dose as naltrexone conjugates with less than 1% as unchanged naltrexone. Plasma level-time data for intravenous naltrexone in six monkeys yielded an average terminal half-life of 7.8 hr and a total body clearance of 64 ml/min/kg. The total body clearance for naltrexone was greater than the hepatic plasma or blood flow in both dogs and monkeys. This finding, together with the extremely low renal excretion of naltrexone, suggests the existence of elimination mechanisms besides liver metabolism and renal excretion.

Animals↗
PubMedDate not supplied

Toxicokinetics/toxicodynamic correlations: goals, methods, and limitations.

Toxicokinetic (TK) studies are the basis for demonstrating dose-related drug exposure in animals and for ensuring that drug exposure is substantially greater in animals than that expected in humans at therapeutic doses. The usefulness of TK studies can be further enhanced by correlating TK parameters with relevant toxicologic end points. The so-called TK/toxicodynamic (TD) correlations can be extremely useful in bridging data from studies both within and across species and in designing early Phase I clinical trials. These correlations assume that toxicologic responses are comparable among species at comparable plasma concentrations. This assumption may apply for certain drugs but not for others. Therefore, TK/TD correlations should be developed and utilized on a case-by-case basis. Such correlations have proven to be extremely useful with anticancer drugs in formulating dose escalation strategies in cancer patients to rapidly attain the maximum tolerated and/or effective dose. However, these correlations have not been utilized effectively in other therapeutic areas. The development of TK/TD correlations, their scope, and limitations are discussed in this paper.

Animals↗
PubMedDate not supplied

Disposition of cefixime in the pregnant and lactating rat. Transfer to the fetus and nursing pup.

The disposition of cefixime, a potent, third generation, orally active cephalosporin, was characterized in the pregnant and lactating rat. After a single iv dose of 17.8 mg/kg 14C-cefixime to day 18 pregnant rats, the half-life for elimination of radioactivity from both maternal serum and placentas was 6.9 hr. Elimination from fetal plasma and tissues was somewhat longer, 12.5 and 13.7 hr, respectively. However, comparison of areas under the curve indicated that exposure of the fetuses to cefixime was far less than that of placentas. Whole body autoradiography showed the greatest radioactivity in maternal liver, kidney, and intestines. In the lactating rat, steady state plasma concentrations of 14C-cefixime were achieved by continuous ip infusion of 2.54 mg/kg/day via Alza osmotic Mini-pumps from days 10 to 14 postpartum. Plasma concentrations of radioactivity in the dams were, on the average, 70 times greater than in their nursing pups throughout the study. After 102 hr of drug infusion, total radioactivity in the body of the pups, including the stomach and intestinal contents, was 1% of the 14C-cefixime estimated to be in the mother's body at steady state. Overall, these data indicate that exposure of the developing rat fetus and nursing pup to cefixime after maternal drug administration is quantitatively small.

Animals↗