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Biomedical subjects

S K Puri

Publications and source records attributed to S K Puri.

At least 91 records · Page 5Linked to original sources
PubMed1989

Infectivity studies on anopheles stephensi using Plasmodium cynomolgi B infection in rhesus monkeys.

The characteristics of primary and secondary asexual peak parasitaemia during sporozoite induced Plasmodium cynomolgi B infections in 40 rhesus monkeys have been studied. Colony bred Anopheles stephensi were fed on different days on the gametocyte carrying monkeys and the infectivity of mosquitoes as determined by oocyst count on day 8 post-feeding was recorded. Following the day of sporozoite inoculation, the mean prepatent period was 8.58 +/- 0.87 days. The primary asexual peak was attained on day 8.38 +/- 2.27 and the secondary peak on day 15.15 +/- 2.63 after patency. Infectivity rate was 100% in 144 batches of mosquitoes fed three days before to three days after the secondary asexual peak. Judging from the day of patency, the high oocyst count was obtained between day 12-18 after patency. Infective gametocyte peak coincided with the secondary asexual peak parasitaemia, with the result that maximum oocyst number was observed in batches fed on the day of secondary peak or one day prior to or one day after the secondary peak. Infectivity during the period of primary asexual peak was inconsistent.

Animals↗
PubMed1989

Effect of a new 8-aminoquinoline antimalarial compound on hepatic microsomal mixed function oxidase system of mice.

A new 8-aminoquinoline derivative (compound 80/53) synthesized at the Central Drug Research Institute, Lucknow (India), has been found to be an active anti-relapse (tissue schizontocidal) compound. Compound 80/53 at 8.75 mg/kg x 4 days and primaquine at 7.00 mg/kg (base) x 4 days given orally to Swiss mice led to inhibition of the different components of the hepatic microsomal mixed function oxidase system to varying degrees. Compound 80/53 inhibited cytochrome P-450, aminopyrine-N-demethylase, aniline and benzo (a) pyrene hydroxylase, cytochrome b5 and heme content of the normal mice by 12, 14, 0, 57, 20 and 6 per cent respectively, whereas the inhibition caused by primaquine in these components was 25, 21, 17, 48, 26 and 6 per cent respectively. Thus, there was less inhibition of hepatic microsomal MFO system of mice by compound 80/53 as compared to that by primaquine.

Aminoquinolines↗
PubMed1988

Pharmacokinetics of roxithromycin (RU 965).

This report contains the findings of five studies performed to evaluate the pharmacokinetics of roxithromycin (RU 965), a new macrolide antibiotic. Roxithromycin was given as 150- and 300-mg film-coated tablets. The drug is rapidly absorbed after oral administration. Peak plasma levels following 150- and 300-mg doses occur within two hours. Steady state is reached within four days with doses of 150 mg twice a day or 300 mg once daily. The plasma half-life is approximately 12 hours. About 10% of the dose is excreted in urine. Although dose dependency was observed for the various pharmacokinetic parameters, dose proportionality could be demonstrated only in terms of the percentage of the dose excreted in urine. The rate of absorption is not affected by age. The rate of elimination and renal clearance are decreased in healthy elderly subjects, however, these differences should not be clinically meaningful. The bioavailability of the drug is not affected to a clinically meaningful extent when it is given with milk. Less than 0.05% of the administered dose is excreted in the breast milk of lactating women. Roxithromycin was safe and well tolerated with no clinically meaningful changes in any of the safety variables in any of the five studies reported.

Adult↗
PubMed1988

Human interferon-gamma protects rhesus monkeys against sporozoite-induced Plasmodium cynomolgi malaria infection.

Earlier we reported that prophylactic treatment with recombinant human interferon gamma (rHuIFN-gamma) for a prolonged duration completely suppressed experimental infection with Plasmodium cynomolgi B sporozoites in rhesus monkeys. We now show that reducing the rHuIFN-gamma treatment to three administrations given close to the time (on days -1, 0, and +1) of infection was sufficient for complete protection. Animals initially protected by rHuIFN-gamma treatment are susceptible to reinfection. Studies are in progress to understand the precise mechanism of protection afforded by HuIFN-gamma against sporozoite-induced malaria infection.

Animals↗
PubMed1988

The pharmacodynamics and pharmacokinetics of multiple doses of the new H2-receptor antagonist, roxatidine acetate, in healthy men.

Roxatidine acetate (HOE 760, TZU 0460) is a new H2-receptor antagonist which is more potent than cimetidine and ranitidine. A randomised, double-blind, placebo-controlled study was conducted in healthy men to determine the effects of multiple oral doses of roxatidine acetate on unstimulated gastric acid secretion, and to assess the preliminary multiple-dose pharmacokinetics of its active desacetyl metabolite. The subjects were randomised to receive either roxatidine acetate 150 mg or placebo daily at 9 pm for 14 days. Gastric secretions were collected by aspiration using a nasogastric tube placed in the distal part of the stomach. Gastric fluid volume, pH, and acid concentrations were determined for 2 hours before drug administration and over 24 hours after administration on days 1, 7, 14 (the last day of dosing), and 17 (3 days after the last dose). Plasma and urine samples were collected throughout the study for the pharmacokinetic assessment. All subjects completed the study without side effects or clinically significant changes in any of the safety variables. Subjects receiving roxatidine acetate had substantial increases in gastric pH and decreases in acid secretion compared to baseline and to placebo-treated subjects. The duration of effect was approximately 12 hours. Nocturnal pH was greater than or equal to 6.0 in 80% of the roxatidine acetate-treated subjects. When sampled 3 days after the last dose (day 17) no differences in pH, acid secretion, or gastric volume were observed between the roxatidine acetate- and placebo-treated groups. The gastric pH increased with the mean plasma concentrations of the desacetyl metabolite. Mean plasma levels at steady state were attained between the 4th and 7th days after which there was no evidence of appreciable accumulation of the desacetyl metabolite. Roxatidine acetate 150 mg administered orally at 9 pm for 14 days to healthy men was safe, well tolerated, and produced clinically relevant increases in gastric pH, and decreases in gastric acid concentration, without affecting gastric fluid volume.

Adult↗
PubMed1987

Roxithromycin: a pharmacokinetic review of a macrolide.

In humans, roxithromycin is rapidly absorbed from the gastrointestinal tract producing peak levels (Cmax) within 2 h. The drug is eliminated with a half-life (T1/2) of about 10 h. Roxithromycin is not extensively metabolized. Approximately 53% is excreted in the faeces and about 10% of the dose is eliminated in urine. Although dose-dependency (with doses from 150 to 450 mg) was observed for certain pharmacokinetic parameters, dose-proportionality could only be demonstrated with urine data. During multiple dosing, steady state is usually reached by day four and is dose-dependent. There is a slight but clinically unimportant increase in the T1/2 of the drug with repeated administration. While the rate of absorption is not affected by age, the rate of elimination and renal clearance are decreased in the elderly subjects. No significant differences were observed for Cmax and Tmax between normal and renally impaired subjects. AUCs and elimination T1/2 were greater, and significantly less drug was excreted in renally impaired patients. In patients with liver cirrhosis Cmax, Tmax, and AUCs are not affected. The bioavailability of the drug is not affected to a clinically important extent when it is given either with milk or food. Less than 0.05% of a single 300 mg dose is excreted in the breast milk of lactating women. After oral dosing a very high concentration of roxithromycin is achieved in pulmonary, prostatic, and tonsillar tissues. However, roxithromycin was not detected in the cerebrospinal fluid of subjects with non-inflamed meninges. It is concluded that 150 mg roxithromycin twice daily or 300 mg once a day should provide plasma levels above the minimum inhibitory concentrations required for antibacterial activity.

Humans↗
PubMed1986

Possible basis for membrane changes in nonparasitized erythrocytes of malaria-infected animals.

Previous studies (Gupta et al. (1982) Nature 299, 259-261) have shown that nonparasitized erythrocytes of Plasmodium knowlesi-infected monkeys contain the procoagulant phospholipid phosphatidylserine (PS) in the outer-half of their membrane bilayer. A reinvestigation of this problem has now revealed that in acute P. knowlesi infection, at least 30% of the infected animals do not have this abnormality. However, PS externalization was a consistent feature in the uninfected red cells of chronically infected animals. Also, a similar membrane change was observed in the red cells of uninfected splenectomized monkeys. These results strongly suggest that spleen plays an important role in maintaining the exclusive inner distribution of PS in the normal erythrocyte membrane, and that partial migration of this lipid to the outer monolayer in nonparasitized erythrocytes could be attributed to an abnormal physiology of this organ in malarial infection.

Animals↗
PubMed1986

Pharmacokinetics of orally administered pentoxifylline in humans.

The pharmacokinetics of pentoxifylline was studied in healthy male volunteers following single oral doses of 100, 200 and 400 mg of the drug in solution. Concentrations of the drug and three of its metabolites were determined in plasma. The major urinary metabolite was also determined for 24 hours after dosing. Pentoxifylline was rapidly and extensively absorbed at all doses. Peak plasma concentrations of pentoxifylline occurred between 0.29 and 0.41 hours after dosing. Its metabolites, a secondary alcohol and two homologous carboxylic acids showed tmax values from 0.72 to 1.15 hours. Cmax and AUC values increased in a dose-dependent manner for pentoxifylline and its metabolites over the three dose levels though strict dose proportionality could only be demonstrated for the principal carboxylic acid metabolite. The apparent plasma half-life of pentoxifylline varied between 0.39 and 0.84 hours for the various doses while the apparent half-lives of the metabolites were in the range of 0.96 to 1.61 hours. The major circulating metabolites, the secondary alcohol and carboxypropyl derivative, were at consistently higher plasma concentrations than the parent drug. Two major pathways account for the circulating metabolites of pentoxifylline though oxidation of the parent drug to a carboxylic acid accounts for the formation of the principal urinary elimination product. Because of the pharmacological activities of pentoxifylline, studies are proposed of the pharmacokinetic-pharmacodynamic correlations of pentoxifylline and its metabolites. The present pharmacokinetic results further support the use of a controlled-release dosage form of pentoxifylline for therapy.

Administration, Oral↗
PubMed1986

Recombinant human gamma interferon inhibits simian malaria.

Prophylactic treatment with 0.1 mg of human gamma interferon per kg (body weight) per day completely suppressed experimental infection with Plasmodium cynomolgi B sporozoites in rhesus monkeys. Treatment with lower doses partially suppressed this infection. Prophylactic treatment with human gamma interferon, however, had no protective effect against trophozoite-induced infection, suggesting that the interferon effect was limited to the exoerythrocytic stage of parasitic development.

Animals↗
PubMed1984

Interactions between oral contraceptives and malaria infections in rhesus monkeys.

The interaction of oral contraceptives with malaria infection (Plasmodium cynomolgi B and P. coatneyi) in adult female rhesus monkeys (Macaca mulatta) was studied. The oral contraceptives (Norinyl and Ovral-28) were administered for 12 consecutive menstrual cycles, from day 5 to 25 of each cycle, at either (1/3) of the human dose of Norinyl (norethisterone 0.33 mg + ethinylestradiol 0.012 mg) or (1/6) of the human dose of Ovral-28 (norgestrel 0.083 mg + ethinylestradiol 0.008 mg).The animals were divided into three groups for each infection (control, Norinyl and Ovral-28 treated) with 10 monkeys in each group for P. cynomolgi B infection and 12 in each group for P. coatneyi infection. The animals were infected after 6 cycles of oral contraceptive administration, and the course of infection was studied during the 7th and 8th cycles. This was followed by radical cure during the 9th and 10th cycles and rechallenge in the 11th and 12th cycles. The present study showed that (1) the contraceptive-treated animals maintained a slightly increased cumulative parasite load; (2) the contraceptives did not interfere with the radical curative action of chloroquine; (3) the contraceptive-treated animals showed no significant change in the course of parasitaemia on rechallenge or in the malaria indirect fluorescent antibody levels; (4) the liver function tests were not altered significantly by the administration of contraceptives and subsequent infection; and (5) the haematological changes observed in the contraceptive-treated animals were similar to those observed in the control group.

Animals↗
PubMed1984

The pharmacokinetics and bioavailability of nomifensine maleate in healthy men.

Two studies were conducted in normal male volunteers to establish the pharmacokinetic parameters for nomifensine maleate and to determine the bioavailability of the drug from the Merital capsule intended for U.S. marketing. Single oral doses of 25, 100, and 200 mg of nomifensine maleate as aqueous solutions were administered to 24 men in the open-label Latin-square design pharmacokinetic study. In the bioavailability study, 24 men received single oral 50 mg doses of nomifensine maleate in a capsule or as an aqueous solution. Plasma levels of nomifensine were determined by radioimmunoassay and urinary levels of total nomifensine and its metabolites were assayed by thin-layer chromatography. There was a proportional increase in the area under the curve (AUC) with increasing dose, while peak plasma levels and amounts of total nomifensine and its metabolites excreted in the urine rose as dose increased. The pharmacokinetics of nomifensine are considered linear over the dose range tested. Nomifensine maleate was equally bioavailable from the 50 mg aqueous solution and the Merital capsule formulation.

Administration, Oral↗
PubMed1982

Clobazam kinetics: intrasubject variability and effect of food on adsorption.

The kinetics of single 20-mg oral doses of clobazam was determined on two occasions in 12 healthy male volunteers. Clobazam was given in the fasting state on one occasion and following a standard breakfast on another. Compared with the fasting state, administration of clobazam with food reduced mean peak plasma concentrations (465 vs. 333 ng/ml, P less than 0.01), and prolonged the time to reach peak concentration (1.7 vs. 2.5 hours after dosage, P less than 0.1). Total area under the curve nor the extent of formation of desmethylclobazam, the major metabolite. Clobazam AUC and elimination half-life each were highly correlated within subjects between the two trials (r = 0.97 and 0.95, respectively). Thus, administration of clobazam with food slows the rate of clobazam absorption but does not alter the completeness of absorption. The rate of drug elimination is highly replicable upon repeated administration clobazam to the same individual.

Adult↗
PubMed1982

Loss of infectivity for Swiss mice of a mefloquine-resistant strain of plasmodium berghei.

A strain of Plasmodium berghei made resistant to a 244 mg/kg daily dose of mefloquine by interrupted subcurative therapy in successive passages in weanling rats, was maintained for more than six months under drug pressure and was cryopreserved. Experiments with this strain have shown its loss of virulence for intact mice. In splenectomized Swiss mice infection with this resistant strain is transient. The mefloquine resistance of this line was unstable and the strain became sensitive to mefloquine after 10 serial drug-free passages but did not recover its infectivity to mice.

Animals↗
PubMed1981

Age-related changes of cyclic nucleotide levels in rat brain regions.

Cyclic AMP and cyclic GMP levels were measured in seven brain areas of rats 4-30 months old. In several brain areas cyclic nucleotides were higher in 4-month-old rats than in rats 12 months old or older. On the other hand, in the hypothalamus cyclic GMP levels were decreased only in 30-month-old rats, a pattern of onset similar to that of senile deterioration.

Aging↗
PubMed1981

Clobazam kinetics in the elderly.

1 The effects of age and sex on the disposition of clobazam (CBZ), a 1.5-benzodiazepine derivative, were evaluated in a series of 29 healthy volunteers aged 18 to 72 years, who ingested single 20 mg oral doses. CBZ kinetics were determined from multiple plasma concentrations measured during 7 days after the dose. 2 CBZ was rapidly absorbed, with peak levels reached an average of 1.5 h after dosing (range 0.5--2.5 h). Mean absorption half-life was 19.7 min. Absorption kinetics were not influenced by age of sex. 3 Elimination half-life ranged from 11 to 77 h, and was significantly longer in elderly v young males (48 v 17 h, P less than 0.01). In women, half-life also increased with age, but differences between young and elderly women were less striking (31 v 49 h, P less than 0.05). 4 Volume of distribution (Vd) was influenced by age and sex. Vd became larger with age regardless of sex, and within each age group was larger in women than in men. Total clearance was unrelated to age in women, but declined significantly with age in men (P less than 0.01). 5 The mean free fraction for CBZ in plasma was 11.5% (range 8.6--15.0%), and tended to increase with age, partly due to a significant age-related decline in plasma albumin concentration (r = -0.68, P less than 0.001). Correction of Vd and clearance for individual differences in binding did not alter their relation to age and sex. 6 As in the case of other benzodiazepines biotransformed by oxidative pathways, the capacity for N-demethylation of CBZ declines with age in men, but age has a minimal effect on CBZ clearance in women.

Adolescent↗