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Biomedical subjects

J Lal

Publications and source records attributed to J Lal.

18 recordsLinked to original sources
PubMed2001

Optimization of contraceptive dosage regimen of Centchroman.

Centchroman (Ormeloxifene), a non-steroidal oral contraceptive, is used at a dose of 30 mg once a week. To prevent failures in the beginning of the therapy, it is recommended that a dose of 30 mg twice a week for 12 weeks be administered to build up adequate blood levels. The present study was undertaken to simplify the dosing schedule without sacrificing the purpose of twice a week dosing regimen, using modeling and measurement approaches. The drug was given to 60 female volunteers who were divided into seven groups: group I, 30 mg weekly; group II, 30 mg twice a week; group III, 30 mg twice a week for 12 weeks followed by 30 mg weekly; group IV, 30 mg twice a week for 6 weeks followed by 30 mg weekly; group V, 60 mg weekly; and groups VI and VII, single 60 mg loading dose followed by 30 mg weekly doses. The blood samples were collected and analyzed by HPLC. In group I, mean trough concentrations of centchroman and its active metabolite, 7-desmethyl centchroman, were comparable to the steady-state trough concentrations in groups III, IV, VI, and VII. The metabolite to parent drug ratio remained constant in all the groups. The pharmacokinetic parameters in group VII were comparable to those reported after a single 30 mg dose. Dosage regimen VI was more convenient and provided better pregnancy protection (Pearl index 1.18; unpublished report) than regimen III, which is currently on the market and, thus, could be effectively used for contraception.

Centchroman↗
PubMed2001

Anti-inflammatory activity of Dalbergia sissoo leaves.

The possible anti-inflammatory activity of the 90% ethanolic extract of Dalbergia sissoo leaves (DSELE) was studied in different models of inflammation in rats after oral administration at doses of 100, 300 and 1000 mg/kg. DSELE significantly inhibited carrageenin, kaolin and nystatin-induced paw oedema, as well as the weight of granuloma induced by a cotton pellet. It also inhibited dye leakage in acetic acid-induced vascular permeability test in mice. DSELE was devoid of ulcerogenic effect on the gastric mucosa of rats in acute and chronic tests. In acute toxicity studies, it was found to be safe up to 10.125 g/kg, p.o. in the rat. It was concluded that the D. sissoo leaf extract possessed significant anti-inflammatory activity (in acute, sub-acute and chronic models of inflammation) without any side effect on gastric mucosa.

Animals↗
PubMed1999

Determination of antifilarial compound UMF-078 and its metabolites in plasma by high-performance liquid chromatography.

UMF-078, methyl (+/-)-[5-(alpha-amino-4-fluorobenzyl)benzimidazol-2-yl]carba mate, is a new antifilarial compound being developed by the World Health Organization. In the present study, a HPLC method for the simultaneous estimation of UMF-078 and its metabolites (flubendazole, decarbamoylated flubendazole, UMF060 and decarbamoylated UMF-060) in plasma was developed, validated and applied to pharmacokinetic studies. Linearity was observed between 20 and 1000 ng/ml for decarbamoylated UMF-060 and between 10 and 500 ng/ml for other analytes. Recoveries were consistent over the concentration ranges studied for all the analytes. Variations in intra- and inter-batch accuracy and precision were within acceptable limits of +/-20% at the lowest limit of quantitation, whereas at higher concentrations it was +/-15%. The analytes showed stability up to two freeze-thaw cycles in plasma. No degradation was observed for any of the analytes even after 72 h of storing the dry plasma extracts at -30 degrees C. The assay method was employed to study the pharmacokinetics of hydrochloride salt of UMF-078 in rats. The parent compound and its metabolites viz: decarbamoylated UMF-060, UMF-060 and flubendazole were quantitated in serum and the compounds could be monitored up to 168 h post-dose.

Animals↗
PubMed1998

Liquid chromatographic determination of a non-steroidal oral contraceptive CDRI-85/287 in rat serum.

A precise and sensitive high performance liquid chromatographic (HPLC) assay method was developed and validated for the quantitation of 2-[4-(2-piperidinoethoxy) phenyl]-3-phenyl-(2H)-1-benzo(b)pyran (compound CDRI-85/287) in rat serum. This method, applicable to 0.5 ml volumes of serum, was validated according to GLP guidelines. It involved double extraction of serum samples with a mixture of hexane and iso-propanol (98:2 v/v) at alkaline pH and the use of UV detection at 332 nm. Linearity, precision and accuracy were acceptable (5-200 ng ml-1. The absolute recovery was more than 75% and the lower limit of quantitation was 5 ng ml-1. Freeze-thaw stability studies up to four cycles showed no apparent differences in the calculated spiked concentrations. However, in-process stability evaluation showed the stability of the processed samples lasted up to 85 h.

Analysis of Variance↗
PubMed1998

Accelerated cyclization of lambda DNA.

In the presence of spermidine, the DNA molecule of the bacteriophage lambda undergoes a coil-globule transition. We report here that the cyclization of this molecule in its globular state is greatly accelerated (by more than 10(4)-fold) in comparison with the cyclization reaction taking place in the coil conformation.

Bacteriophage lambda↗
PubMed1995

Pharmacokinetics of centchroman in healthy female subjects after oral administration.

The pharmacokinetics of centchroman, a non-steroidal antifertility agent, were assessed in serum of eleven healthy female subjects after a single 30 mg oral dose. Maximum serum concentration (Cmax) of 55.53 (s.d., 15.45) microgram/L was attained at 5.18 (s.d., 1.78) h after oral administration. The concentration-time profile was best described by a two-compartment open model with bi-exponential disposition functions. The mean terminal elimination half-life (t1/2) was 165 (s.d., 49) h with a clearance of 6.17 (s.d., 1.67) L/h and volume of distribution of 1420 (s.d., 478) L. Comparison of the pharmacokinetic parameters of this study with those obtained after a single 60 mg oral dose did not show statistically significant differences in the rate of absorption, distribution and elimination. The Cmax and AUC0-infinity were dose-dependent. Thus, the absorption and disposition of centchroman are of first-order, reproducible and dose-dependent.

Administration, Oral↗
PubMed1995

Centchroman: a new non-steroidal oral contraceptive in human milk.

Centchroman, a non-steroidal oral contraceptive drug, was given to 13 nursing mothers comprising two groups. Each participant in group I (n = 8) received a single 30 mg dose, and in group II (n = 5) each participant received a 30 mg twice a week dose for twelve weeks. Simultaneous blood and milk samples were collected and analyzed for the parent drug by high performance liquid chromatography. In the single dose study (group I), the mean +/- peak centchroman concentrations in milk and serum were 78.7 +/- 28.4 and 63.6 +/- 23.6 ng/ml with milk-to-serum (M/S) ratio of 1.4 +/- 0.9. There was no significant increase in centchroman concentrations in milk after multiple dosing (group II). However, serum concentrations reached up to 112.5 ng/ml at 6 h after the 13th dose. Average M/S ratios were insignificantly different at trough (prior to next dose) and at peak (4-6 h after dose) centchroman levels. Additionally, the breast milk and serum centchroman concentrations showed a significant correlation (r = 0.64, P < 0.01), indicating that the amount of centchroman excreted into breast milk is dependent on serum concentrations. The weekly dose (% of the maternal dose) of centchroman ingested by the breast-fed infant at peak maternal serum and milk levels was in the range of 0.4 to 11.5%, assuming a weekly milk uptake of 1.05 l/kg. There was no significant difference in the dose ingested by the infants between the two dosing groups. These levels of centchroman passing into breast milk and subsequent exposure to the infants are unlikely to be of any physiological consequence.

Administration, Oral↗
PubMed1994

Simultaneous liquid chromatographic determination of centchroman and its 7-demethylated metabolite in serum and milk.

A precise and sensitive high-performance liquid chromatographic assay was developed and validated for determination of centchroman (I) and its 7-demethylated metabolite (II) in human serum and milk. The serum, at alkaline pH, was extracted with diethyl ether. In the case of milk, after precipitation of the milk protein with acetonitrile, the supernatant was evaporated to dryness and then extracted with diethyl ether at alkaline pH. After solvent evaporation the residue was reconstituted in mobile phase. Separations were accomplished by reversed-phase liquid chromatography using a Spheri-5 cyano column. Recoveries of I and II were always > 95%. Excellent linear relationships (r > 0.999) were obtained between the measured and added concentration ratios of the corresponding serum and milk concentrations over a range of 1 to 1000 ng/ml and 2.5 to 1000 ng/ml for I and II, respectively.

Acetonitriles↗
PubMed1994

Determination of ampicillin in serum by high-performance liquid chromatography with precolumn derivatization.

A high-performance liquid chromatographic assay method using precolumn derivatization and fluorescence detection has been developed and validated for the determination of ampicillin in serum. The presented method is simple and provides improved selectivity and sensitivity over other existing HPLC methods. It is linear over the concentration range of 100 to 10,000 ng/ml (method 1) and 2 to 1000 ng/ml (method 2) and the extraction recovery is more than 75%. The coefficient of variation is found to be less than 10% over the concentration ranges studied.

Ampicillin↗
PubMed1994

Pharmacological effects of Azadirachta indica (neem) leaf extract on the ECG and blood pressure of rat.

Neem leaf alcoholic extract (NLE) was investigated for its effects on the ECG and blood pressure of rat. Intravenous administration of NLE (100, 300 and 1000 mg/kg) resulted in initial bradycardia followed by cardiac arrhythmia in rats. NLE produced a significant and dose-related fall in blood pressure which was immediate, sharp and persistent. Pre-treatment with either atropine or mepyramine failed to prevent the hypotensive effect of NLE.

Animals↗
PubMed1986

Comparative antitussive effects of dextrorphan, dextromethorphan and phencyclidine.

The possible antitussive effects of dextrorphan (the (+) isomer of levorphanol) and phencyclidine (PCP) were compared to well known antitussive properties of dextromethorphan in the post-halothane anesthetized decerebrate cat in which cough was elicited by direct electrical stimulation of the cough center. Dextrorphan, when injected i.a. (0.05-0.32 mg kg-1) or i.v. (1 to 3 mg kg-1), PCP i.a. (0.1-0.32 mg kg-1) or i.v. (1.0 mg kg-1) had no effect on electrically elicited cough. After i.v. administration, dextrorphan caused a variable effect on respiration but did not have any respiratory effect with i.a. administration of the drug. PCP injection i.a. at 0.32 mg kg-1 severely inhibited respiration though coughing could still be elicited. But i.v. administration of 1.0 mg/kg-1 suppressed both cough and respiration for several hours. Dextromethorphan inhibited cough upon both i.a. and i.v. injection. The mean effective i.a. dose was 0.063 mg kg-1. A ten times higher dose was necessary (0.65 mg kg-1) for cough suppression by the i.v. route. It is concluded from the i.a./i.v. ratio that dextromethorphan has specific central antitussive activity not possessed by dextrorphan and PCP.

Animals↗
PubMed1985

Involvement of the renin-angiotensin system in the dipsogenic effect of morphine.

This paper examined whether drinking elicited by morphine is dependent upon an intact renin-angiotensin system. Bilateral nephrectomy, carried out one day prior to administration of morphine, completely abolished morphine-induced water intake, pointing to involvement of the kidneys in the dipsogenic effect of morphine. Plasma and renal renin depletion were induced by the clipping of one renal artery followed, one month later, by removal of the clipped kidney. In such renin-depleted rats with subnormal plasma renin levels, morphine and isoprenaline-induced water intakes were linearly related to pre-injection basal plasma renin level. Such a relationship was not found in rats with normal renin levels. These results pointed to the existence of a permissive interaction between morphine and the renin-angiotensin system. Captopril, an inhibitor of the angiotensin converting enzyme, increased morphine-induced water intake. We interpreted this drinking response as being the sum of morphine-induced drinking (following a permissive interaction between morphine and circulating angiotensin I or renin) and captopril-induced drinking (following a captopril-induced increase in circulating renin and angiotensin I levels). The competitive antagonist of angiotensin II, saralasin, had no effect on morphine-induced drinking. This result pointed once again to a permissive interaction between morphine and circulating angiotensin I or renin.

Animals↗
PubMed1985

Evidence for a central site of action for the antitussive effects of caramiphen.

The antitussive properties of caramiphen edisylate were studied in the decerebrate cat in which cough was elicited by direct electrical stimulation of the cough center. In this preparation dextromethorphan hydrobromide was compared to caramiphen as an antitussive agent. Dextromethorphan was somewhat more potent when given i.v. as well as when given directly into the left vertebral artery (i.a.). Both agents were far more effective when given i.a. than when given i.v. The effective dose ratios of i.v./i.a. were about 12 and 14 for caramiphen and 11 and 7 for dextromethorphan (actual and cumulative doses). These ratios indicate that both agents have a central rather than a peripheral site of antitussive action. Both drugs had antitussive effects in i.a. doses which did not alter arterial blood pressure or respiration greatly. However, after i.v. administration transient changes in both arterial blood pressure and respiration were observed with both agents. It was concluded that the antitussive action of both caramiphen and dextromethorphan is due to a selective effect on the cough center in the brainstem of the cat. On a milligram per kilogram basis, caramiphen required a 3 to 4 times larger dose than dextromethorphan for equieffective antitussive effects.

Animals↗
PubMed1984

Possible role of prostaglandins in the regulation of food intake in the newborn rat.

The effect of fatty acids (prostaglandins, arachidonic and linoleic acids) and prostaglandin synthetase inhibitors on food intake (measured as change in weight) were studied in newborn and young rats. PGE2 (0.1, 0.5 mg/kg) and PGF2 alpha (0.5 mg/kg) inhibited feeding in the 6 hr deprived 1 day old rat. Under the same deprivation PGF2 alpha (0.5, 1 mg/kg) also caused anorexia in 5, 10 and 15 day old rats. S.C. injection of arachidonic acid (2.5-20 mg/kg) and linoleic acid (150 mg/kg) depressed while aspirin (200-400 mg/kg) and indomethacin 8-32 mg/kg) increased feeding in the non-deprived 1 day old rat. The anorectic activity of arachidonic acid is antagonized by prior (1 hr) administration of aspirin (100 mg/kg) and indomethacin (4 mg/kg) indicating the involvement of prostaglandins in arachidonic acid-induced anorexia. S.C. injection of aspirin (400 mg/kg), indomethacin (4,8 mg/kg) and flurbiprofen (3.12-25 mg/kg) to 1.5 hr deprived 5 day old rats also increased food intake. It is hypothesized that the prostaglandin-generating system and endogenous aspirin (endospirin)-like substances, which inhibit such a generation, play an important physiological role in the regulation of hunger-satiety in the newborn rat.

Animals↗