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Biomedical subjects

K Krishnaswamy

Publications and source records attributed to K Krishnaswamy.

At least 73 records · Page 4Linked to original sources
PubMed1982

Pharmacokinetics and plasma steady state levels of doxycycline in undernutrition.

1 The kinetics of doxycycline were studied in well nourished and undernourished male subjects. 2 The area under the curve after an intravenous dose was reduced and total body clearance was significantly elevated with a shorter/beta-phase half life of the drug in undernourished subjects. 3 The percentage of total drug excreted in urine in 48 h and renal clearance of the drug were similar in both groups. 4 Plasma protein binding was significantly reduced and gamma-glutamyltransferase levels tended to be higher in the undernourished as compared to normals. 5 Increased total body clearance of the drug appeared therefore to be due to higher metabolism of drug in undernourished subjects. This increased metabolism is probably due to lower protein binding of the drug and/or induction of drug metabolism. 6 Plasma Cmin concentrations of doxycycline determined at steady state were lower in undernourished subjects. However, they were within the therapeutic range. 7 The observed alterations in kinetics of doxycycline therefore do not warrant a change in dosage regimen in undernourished subjects.

Adult↗
PubMed1982

Pharmacokinetics of tetracycline in nutritional edema.

Tetracycline pharmacokinetics were studied in a group of normal subjects and in patients with nutritional oedema. Though both groups of subjects received similar dose per kilogram body weight, plasma concentrations and area under the curve (AUC) were significantly higher in nutritional oedema patients. The total body clearance of the drug was reduced due to significant reductions in renal and non-renal clearance of drug. The volume of distribution (VB) was low, with significant increase in rate of transfer of drug from peripheral to central compartment (K21), indicating poor tissue sequestration of the drug in nutritional-oedema patients. In some respects, these alterations in kinetics of tetracycline in nutritional-oedema patients are different from our earlier observations made in undernourished subjects who had mild and moderate forms of malnutrition. These results suggest that changes in disposition of drugs are also influenced by the severity of malnutrition, and demand suitable alterations in dosage regimen.

Edema↗
PubMed1981

Glutathione and gamma-glutamyl cycle enzymes in human fetal liver.

Human fetal and adult liver were found to have similar concentrations of acid soluble sulfhydryl (SH) groups (7.4 mmol/kg) in the same range as is found in adult mouse and rat liver. The concentration was 4-fold higher than in human fetal adrenal gland tissue. Methods specific for glutathione (GSH) associated SH groups revealed that the postmortem levels of GSH is very low (0.4 mmol/kg) in relation to total SH groups. In contrast, the levels of cysteine were high (2.8 mmol/kg), indicating a rapid cleavage of GSH. Only negligible amounts of gamma-glutamylcysteine and cysteinylglycine were measured. Our findings may be explained by high fetal activity of gamma-glutamyl transpeptidase (which metabolizes GSH) that has been documented previously both in man and in experimental animals. High activities of the two GSH-synthesizing enzymes, gamma-glutamylcysteine synthetase and GSH synthetase were found in the human fetal liver (7.1 and 3.0 mukat/kg, respectively). The activities of these enzymes were in the same range as in human adult liver, whereas that of gamma-glutamyl transpeptidase was 3-fold higher in the fetal liver. Our results demonstrate the presence of high concentration of SH groups and capacity to synthesize GSH already in the first and second trimester of the human fetal gestation. This has more than theoretical interest, since we assume that the SH groups (GSH) have importance for the protection of the fetus against drugs and foreign compounds and their (toxic) metabolites, the formation of which is catalyzed by the fetus itself.

Adrenal Glands↗
PubMed1981

Tetracycline absorption in malnutrition.

Tetracycline absorption was studied in a group of normal healthy subjects and in adult male patients suffering from various nutritional disorders such as protein-calorie malnutrition, pellagra, anaemia, and vitamin B-complex deficiency. Tetracycline hydrochloride in doses of 10 mg/kg body weight was administered in a crossover design by oral and intravenous routes at an interval of one week. Absorption of tetracycline was determined from total 48-hour urinary excretion of the drug following each dose. It was observed that tetracycline absorption was significantly reduced in subjects with undernutrition and pellagra but not in patients with orolingual lesions due to vitamin B-complex deficiency and in patients with severe anaemia. Comparative studies on absorption of tetracycline, given in the form of capsule and solution, indicated that impaired absorption of tetracycline in undernourished subjects was not due to inadequate dissolution of the capsule.

Adult↗
PubMed1981

Tetracycline kinetics in undernourished subjects.

The pharmacokinetics of tetracycline were studied in eight normal healthy adult male volunteers and six undernourished adult males, ages 25-40 years, after an intravenous dose of 10 mg/kg body wt. The post-intravenous tetracycline time curve was found to decline in a biphasic manner in both well-nourished and undernourished subjects. However, significant differences were observed in alpha and beta phase with significant alterations in microscopic rate constants and apparent volume of distribution. The kinetic constants suggested a rapid distribution with a faster rate of transfer of drug between compartments followed by a significant increase in total body clearance in undernourished subjects. The apparent volume of distribution was significantly reduced. It is concluded that due to alterations in kinetics undernourished subjects may require altered dosage regimens to maintain tetracycline concentrations above the recommended minimum inhibitory concentration in both plasma/tissue for effective therapy.

Adult↗
PubMed1979

Metabolism of drugs and carcinogens in man: antipyrine elimination as an indicator.

The suitability of the most commonly used "prototype" drug, viz, antipyrine, in predicting drug and carcinogen metabolism was evaluated, by studying in vivo antipyrine elimination rate (Ke) and in vitro metabolism of drugs and carcinogens in liver preparations in the same individuals. Our subjects were 20 adult males undergoing abdominal surgery for gastrojejunostomy, although antipyrine Ke could be studied in only 16 subjects. Correlations of the various in vito--in vivo parameters were positive between the parameter pairs: in vivo antipyrine Ke--in vitro benzopyrene hydroxylase; benzopyrene hydroxylase--aniline hydroxylase; and benzopyrene hydroxylase--gamma-glutamyl transferase. Aminopyrine demethylase did not correlate with any of the parameters studied. The degree of correlation between antipyrine Ke and benzopyrene hydroxylase was statistically significant but was not satisfactory for predictive purposes. Our study indicates some of the problems and limitations of in vivo--in vitro comparisons and confirms earlier doubts on the usefulness of antipyrine as a "prototype" drug for predicting drug and carcinogen metabolism in man.

Adult↗
PubMed1979

Metabolism of sulphadiazine in malnutrition.

1. The kinetics of sulphadiazine were studied in well-nourished and under-nourished subjects. 2. The metabolic clearance rate of a single dose of sulphadiazine given either orally or intravenously was faster in under-nourished subjects. 3. The plasma protein binding of the drug was found to be reduced in under-nourished subjects. 4. Blood concentrations (48 h and 72 h) of sulphadiazine tended to be low in the under-nourished as compared with well-nourished subjects after administration of multiple doses of the drug. 5. It is concluded that a revision in the dosage schedule may not be necessary in the treatment of under-nourished subjects with sulphadiazine, since the blood concentrations were higher than the reporte d minimum to combat infection.

Adult↗
PubMed1978

Effect of leucine at different levels of pyridoxine on hepatic quinolinate phosphoribosyl transferase (EC 2.4.2.19) and leucine aminotransferase (EC 2.6.1.6) in rats.

1. Effects of incorporating 30 g leucine/kg into diets on quinolinate phosphoribosyl transferase (QPRT; EC 2.4.2.19) activity and leucine aminotransferase (EC 2.6.1.6) activity were studied in groups of rats receiving 5, 30 and 60 micrograms of pyridoxine/10 g diet. 2. The results indicated that 30 g leucine/kg diet significantly reduced the QPRT activity when the diets provided 5 micrograms pyridoxine/10 g and that the effect was only marginal when the diet included 30 micrograms pyridoxine/10 g. The inhibitory effect was completely absent when the diet provided higher amounts of pyridoxine (60 microgram/10 g). 3. These results suggest that additional amounts of pyridoxine are necessary to counteract the effects of excess of leucine in the diet. 4. Leucine aminotransferase activity was increased in rats given diets containing higher amounts of pyridoxine; supplementary leucine also increased the enzyme activity.

Animals↗
PubMed1978

Vitamin B6 nutritional status of pellagrins and their leucine tolerance.

Disturbances in tryptophan-nicotinamide adenine dinucleotide pathway, seen in pellagrins whose staple is sorghum have been ascribed to an amino acid imbalance caused by excess intake of leucine. Studies in normal human volunteers and in experimental animals have shown that administration of vitamin B6 will counteract some of the metabolic effects of leucine. In view of these observations, two clinical studies were conducted--one to investigate the vitamin B6 nutritional status of pellagrins and the other to determine whether plasma leucine clearance in pellagrins is different from that of normals. Vitamin B6 nutritional status of pellagrins was found to be far from satisfactory, as indicated by elevated levels of xanthurenic acid and kynurenic acid in urine after a tryptophan load and low plasma pyridoxal phosphate levels. Plasma leucine concentrations at 1, 2, and 4 hr after a leucine load were significantly higher in pellagrins than those in normals. Administration of 25 mg of vitamin B6, intramuscularly 30 min before leucine load significantly decreased plasma leucine concentration in pellagrins. However, the leucine concentration at 4th hr did not return to basal level. Administration of vitamin B6 10 TO 20 mg/day orally for 10 to 15 days normalized leucine tolerance in pellagrins. Data presented here suggest that when the diets contain excess leucine, additional amounts of vitamin B6 are required.

Adult↗
PubMed1978

Streptomycin pharmacokinetics in malnutrition.

Pharmacokinetic parameters of streptomycin such as plasma concentration, plasma half-life, urinary excretion, and in vitro and in vivo binding to plasma proteins were studied in undernourished and well-nourished individuals. None of the parameters studied were different in undernourished subjects as compared to those in well-nourished, in spite of significant differences in mean albumin values between the two groups. This may be attributed to unaltered protein binding of the drug in undernourished subjects in spite of low serum albumin levels, since streptomycin binds to globulins, in addition to albumin.

Adult↗
PubMed1977

Influence of nutritional status on plasma levels and relative bioavailability of tetracycline.

Relative bioavailability after oral administration of a single dose and Cmin levels of tetracycline in plasma after multiple doses were determined in groups of well-nourished and under-nourished subjects. The relative bioavailability of tetracycline, assessed by the area under serum concentration time-curves, did not differ in under-nourished and well-nourished patients. The plasma levels were not different in the two groups after the conventional dose of tetracycline HCL 250 mg at 6 hour intervals. However, in these studies under-nourished subjects received a higher dose per kg body weight, which could have compensated for any effect of a shortened half life of the drug. When the dose per kg body weight was reduced, the Cmin levels were lower. On the other hand, with the same dose per kg body weight at more frequent intervals, the plasma concentrations were similar to those in well-nourished subjects. These studies indicate that the dosage regimen should be based both on body weight and on the nutritional status of the individual.

Adult↗
PubMed1977

Microsomal enzymes in malnutrition as determined by plasma half life of antipyrine.

Nutritional-pharmacological interactions were studied in a group of malnourished subjects. Antipyrine was used to evaluate mixed-function oxidase in man. The results indicated that the rate of disappearance of antipyrine from plasma was strongly influenced by the nutritional status of the individual. The half life of antipyrine was modified in undernourished subjects and those with nutritional oedema. This finding indicates that drug regimens may have to be adjusted in patients who have antipyrine half lives that are shorter or longer than normal. Otherwise drug treatment may be inadequate or, in patients with impaired microsomal enzyme activity, potentially dangerous.

Anthropometry↗
PubMed1977

Failure to produce atherosclerosis in Macaca radiata on a high-methionine, high-fat, pyridoxine-deficient diet.

Accelerated atherosclerotic lesions are observed in genetic defects characterised by marked homocystinaemia as a result of low levels of cystathionine synthase, a pyridoxal phosphate-dependent enzyme. Attempts were therefore made to induce atherosclerosis in Macaca radiata, maintained on a high-protein, high-methionine and high-fat diet by inducing pyridoxine deficiency with deoxypyridoxine. Pyridoxine deficient monkeys failed to show any biochemical or pathological evidence of atherosclerosis, despite a significant decrease in the activity of hepatic cystathionine synthase.

Alanine Transaminase↗
PubMed1977

Functional significance of low serum vitamin B12 levels in pregnancy.

The physiological significance of low levels of vitamin B12 in serum in late pregnancy was assessed by a functional test viz. urinary excretion of methylmalonic acid (MMA) after a valine load. This was normal in all but one subject despite low levels of vitamin B12 in serum in many of these subjects. Assay of serum vitamin B12 levels in pregnant women and control subjects by two different techniques viz. radio isotope dilution and microbiological methods gave essentially similar results for both groups, although the absolute values in both the groups were over-estimated by the former technique. The data presented indicate that there is no evidence of functional inadequacy in pregnant women with low levels of vitamin B12 in serum.

Biological Assay↗