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V Batra

Publications and source records attributed to V Batra.

29 records · Page 2Linked to original sources
PubMed1995

Pharmacokinetic-pharmacodynamic (PK-PD) modeling for a new antihypertensive agent (neutral metalloendopeptidase inhibitor SCH 42354) in patients with mild to moderate hypertension.

SCH 42354, a neutral metalloendopeptidase (NEP) inhibitor, is the pharmacologically active form of the prodrug SCH 42495. It exerts antihypertensive effects by potentiating atrial natriuretic peptide (ANP) activity through inhibition of its hydrolysis by NEP. The objective of this study was to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of SCH 42354 in hypertensive males. SCH 42495 12.5 to 400 mg was administered orally to hypertensive men twice daily in a double-blind, placebo controlled multiple-dose parallel group design. Plasma SCH 42354 concentration and diastolic blood pressure (DBP) data were used to develop a PK-PD model using two approaches. In the first (non-integrated) approach, the ¿link¿ model was used to predict effect-site concentrations, and was applied to data obtained at the 300 and 400 mg BID doses only; data at the other (lower) doses were not amenable to modeling because of high variability. Effect-site concentration and DBP data were then fit to a sigmoid Emax PD model. For the 300 mg BID dose, PD parameters were: maximum effect (Emax), 8.1 mmHg; no-drug effect (Eo), 3.6 mmHg; concentration corresponding to 50% of maximum response (EC50), 0.87 microgram x ml(-1); and gamma, 3.9. In the second (time-integrated) approach, plasma SCH 42354 concentration and effect data obtained over the entire dose range were integrated with respect to time. Average plasma concentration and DBP data were then fit to a simple Emax PD model. PD parameters obtained over the dose range were: Emax, 10.3 mmHg; Eo, 2.0 mmHg; and EC50 0.7 microgram x ml(-1). These were similar to the estimates obtained from the first approach, demonstrating that the integrated (average) data allow PK-PD modeling over the (entire) dose range. The analysis showed that, at steady-state, a 400 mg BID dose of SCH 42495 produced an approximate 10 mmHg decrease in DBP in hypertensive males; the average plasma SCH 42354 concentration attained at this dose was approximately 1.8 microgram x ml(-1).

Adult↗
PubMed1995

Pharmacokinetics of ceftibuten in children.

The bioavailability and pharmacokinetics of ceftibuten administered as an oral suspension were characterized by several studies in young healthy male adults (19 to 39 years old) and children ranging in age from 6 months to 17 years. Ceftibuten suspension was found to be bioequivalent and thus interchangeable with a standard 400-mg capsule. As with the capsule formulation, food slightly (< 20%) affected the rate and extent of absorption of the suspension. The recommended dose of 9.0 mg/kg was found to produce comparable plasma concentrations in children of all ages (6 months to 17 years). The range of mean values of maximum plasma concentrations (Cmax) was 12 to 16 micrograms/ml at the 9.0-mg/kg dose level. Doses of 4.5, 9.0 and 13.5 mg/kg produced Cmax and area under the plasma concentration-time curve values that were dose-proportional. The half-life (t1/2) was essentially independent of age and dose, ranging from 2 to 3 hours. The apparent clearance (Cl/F), uncorrected for the fraction of drug absorbed (F), is independent of dose but appears to increase with a decrease in age. This also occurs to a lesser degree with the volume of distribution (Vd/F), uncorrected for F. Current evidence suggests that this is more likely to be caused primarily by a decrease in F than an increase in Cl. Ceftibuten rapidly and extensively reaches the middle ear fluid in children with acute otitis media. Within 4 hours concentrations in middle ear fluid are similar to plasma concentrations and can be measured for 12 hours. The ratio of area under the concentration time curve for middle ear fluid relative to plasma was about 70%.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1995

Pharmacokinetics and metabolism of 14C-isepamicin in humans following intravenous administration.

Twelve healthy adult male volunteers received 1 g (base equivalent) of 14C-isepamicin (131 microCi) as an intravenous bolus over 5 min. The areas under the plasma concentration-time curves at infinity for isepamicin (196 micrograms*h/ml) and total radioactivity (164 micrograms*h/ml) were similar, indicating no biotransformation of isepamicin. The disappearance of isepamicin from plasma followed a triexponential decline, with half-lives of 0.17, 2.12, and 34 h for the alpha, beta, and gamma phases, respectively. However, the contribution of the gamma phase to the total area under the concentration-time curve was only 2.6%. There were no detectable metabolites in plasma and urine, confirming that isepamicin was not biotransformed. The cumulative levels of isepamicin and total radioactivity excretion in urine from 0 to 120 h were 97.3 and 92.1% of the dose, respectively, indicating that the drug was excreted mainly as unchanged isepamicin in urine.

Adult↗
PubMed1995

Tone-dependent responses of histamine in feline pulmonary vascular bed.

Under conditions of controlled pulmonary blood flow and constant left atrial pressure, histamine produced tone-dependent responses in the pulmonary vascular (PV) bed of intact-chest, spontaneously breathing cats. At low, baseline PV tone, histamine produced dose-dependent increases in mean lobar arterial pressure that were antagonized by the selective histamine H1-receptor antagonist, diphenhydramine. The cyclooxygenase inhibitor, meclofenamate, and the thromboxane A2 (TxA2) receptor antagonist, SQ-29548, had no effect on these vasoconstrictor responses of histamine. After an increase in PV tone with an intralobar arterial infusion of a TxA2 mimic, U-46619, histamine produced vasodilator responses at low doses, biphasic vasodilator/vasoconstrictor responses at midrange doses, and vasoconstrictor responses at high doses. Diphenhydramine antagonized vasoconstrictor responses and the vasodilator responses of low to midrange doses and enhanced vasodilator responses of high doses of histamine at elevated PV tone. Selective H2-receptor antagonists, ranitidine and meclofenamate, and selective H3-receptor antagonist, thioperamide, did not antagonize vasodilator responses of histamine. H1- and H2-receptor antagonism was more effective in reducing the vasodilator responses of histamine at elevated PV tone than H1-receptor antagonism alone. These data support that histamine produces vasoconstrictor responses at low baseline and elevated PV tone by acting on H1 receptors that do not induce the release of vasoconstrictor prostanoids. At elevated PV tone, histamine produces vasodilation by acting on H1 receptors that are not coupled to the release of vasodilator prostaglandins and also, in part, by acting on H2 receptors.

Animals↗
PubMed1994

Sustained release of ferrous sulfate from polymer-coated gum arabica pellets.

Sustained release of ferrous sulfate (FeSO4) from gum arabica pellets has been achieved for 7 h. Release is further sustained for 12 to 600 h by coating the pellets with polyvinyl acetate and ethylene vinyl acetate, respectively. An increase in the amount of gum arabica in the pellets decreases the rate of release due to the gelling property of gum arabica. The gel layer acts as a barrier and retards the rate of diffusion of FeSO4 through the pellet. In coated pellets, an increase in thickness of membrane helps to sustain the release of FeSO4 for a longer duration. Thus, the release of FeSO4 can be sustained for the required duration by adjusting the amount of gum arabica in the pellet and the composition and thickness of polymeric coat. The mechanism of release accordingly varies from Fickian to zero-order and super case II transport.

Chemical Phenomena↗
PubMed1992

Paraganglioma of the cauda equina.

A case of paraganglioma of the cauda equina is presented. Usually reported to be benign with good prognosis, the present patient had a somewhat different course. The behaviour of the tumour was unusual, with rapid recurrence seen within first month of surgery. The need for total surgical excision and role of adjuvant radiotherapy is highlighted.

Cauda Equina↗
PubMedDate not supplied

Epidemiology of chronic suppurative otitis media and deafness in a rural area and developing an intervention strategy.

Of 613 children evaluated in a village in Haryana 94 (15.3%) were observed to have chronic suppurative otitis media (CSOM). Fifty eight (61.7%) children had hearing impairment. CSOM contributed to 71.6% of the hearing impaired (58/81). On analysis of association of CSOM with literacy and socio-economic status of mothers, and age, sex, and upper respiratory tract infections (URI) in children positive correlation was observed only with URIs (P < 0.001). Literacy and socio-economic status of the mothers did not correlate significantly with knowledge about treatment seeking, and ear cleaning practices, probably due to the narrow range of incomes and literacy levels. An intervention program consisting of play, demonstrations, health charts and slogans, and aural cleaning and antibiotic drops was introduced.

Adolescent↗
PubMedDate not supplied

Comparative pharmacokinetics of 14C-piperacillin following intravenous and intraperitoneal administration in pregnant and non-pregnant rats.

14C-piperacillin (Pipracil) at a dose level of 1000 mg/kg was administered intravenously or intraperitoneally to pregnant and non-pregnant female rats. Rats were sacrificed at predetermined time intervals, and 14C-piperacillin concentrations determined in serum, amniotic fluid, placenta, and fetus. The piperacillin serum levels in both pregnant and nonpregnant rats following intravenous administration were comparable; however, following intraperitoneal administration, the serum drug levels in the pregnant rats as compared to the nonpregnant rats were lower. The fetal drug levels, however, were higher following intraperitoneal administration than following intravenous administration. The total area under the fetal drug concentration-time curve following intraperitoneal administration was about two times the corresponding area under the curve following intravenous administration. The data indicate that the fetal exposure to piperacillin was greater following intraperitoneal administration.

Amniotic Fluid↗