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A M Hoyumpa

Publications and source records attributed to A M Hoyumpa.

At least 19 recordsLinked to original sources
PubMed1990

Thiamine-transfer by human placenta: normal transport and effects of ethanol.

Transport of "physiologic" concentrations of thiamine by the normal, term human placenta was studied by using the perfused cotyledon technique. Thiamine, 50 nmol/L, crossed from the maternal to fetal compartment at a rate somewhat below that of antipyrine, a freely diffusible marker drug. The transport was saturable and inhibited by structural analogues of thiamine, implying participation of carriers. Thiamine accumulated in the fetal compartment against a concentration gradient, suggesting active transport. Consistent with this, transfer of thiamine from the fetal to maternal compartment was significantly lower than in the opposite direction. The vitamin was concentrated in the placenta when compared with maternal and fetal levels. There was no evidence of phosphorylation of thiamine during its transfer. Exposure of the placenta to ethanol, 400 mg/dl, for up to 4 hours did not alter maternal-to-fetal transfer of the vitamin.

Antipyrine↗
PubMed1989

Effects of liver disease on the disposition of ciramadol in humans.

To determine the effects of liver disease on the disposition of ciramadol, an analgesic that undergoes ether glucuronidation, we studied its plasma pharmacokinetics in 10 patients with stable cirrhosis, 8 with acute viral hepatitis, and 16 age-matched healthy controls. Renal excretion of the glucuronides was also determined. In healthy controls given a single intravenous dose of the drug the t 1/2 was 3.4 +/- 0.3 hrs and the systemic clearance was 668 +/- 109 ml/min of which renal clearance was 320 +/- 73 ml/min and non-renal clearance 349 +/- 74 ml/min. The corresponding values after an oral dose were similar. Renal clearance was related directly to the estimated creatinine clearance. Moreover, the renal clearance of ciramadol exceeded creatinine clearance, suggesting that the drug was excreted not only by glomerular filtration but also by tubular secretion. The systemic clearance of intravenous ciramadol was diminished by 40% in cirrhosis, P less than 0.05, due to a reduction in renal clearance, while non-renal clearance remained normal. Renal clearance of the inactive glucuronides, on the other hand, was not affected. In patients with acute viral hepatitis, systemic clearance was unchanged, but renal clearance of ciramadol tended to increase during the acute phase of the disease and to return toward normal after recovery. Renal excretion of the inactive glucuronides was decreased by 48% (P less than .05). These findings suggest that the non-renal ether glucuronidation of ciramadol remains intact in patients with stable cirrhosis or acute viral hepatitis. However, the renal clearance of the drug may be impaired in cirrhosis, but tends to be enhanced in acute hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Hepatic oxidative drug metabolism and the microsomal milieu in a rat model of congenital hyperbilirubinemia.

The aims of this study were to evaluate the hypothesis that impaired glucuronidation of bilirubin and possibly of drug oxidation in the liver of homozygous (jj) Gunn rats may be due to an altered microsomal milieu. Accordingly, we investigated and compared in vivo and in vitro demethylation of aminopyrine, hepatic cytochrome P-450 levels, microsomal lipid composition, and microsomal membrane fluidity in icteric, homozygous (jj) Gunn rats and in their anicteric heterozygous (jJ) littermates. In both males and females, [14C]aminopyrine demethylation in vivo, using the 14CO2 breath test, was unimpaired in the icteric animals. Likewise, cytochrome P-450 levels in the icteric and nonicteric groups were similar, and aminopyrine kinetics in vitro in the females were comparable in icteric and nonicteric littermates. The main lipid classes were also similar in the homozygous and heterozygous female Gunn rats, whereas only minor changes were seen in the phospholipid fatty acyl composition with a small, but significant, increase in the unsaturated index in the icteric group. Despite this, there was no apparent effect on hepatic microsomal membrane fluidity as measured by the order parameter of I[12,3] and the rotational correlation time of I[1,14] in either female or male sets of homozygous and heterozygous Gunn rats. Our data, therefore, do not support an alteration of composition or fluidity of the microsomal milieu as a mechanism of impaired bilirubin glucuronidation and possibly of oxidation in these animals. They also absolve long-term unconjugated hyperbilirubinemia as a mechanism of hepatic microsomal dysfunction. Our study, therefore, indirectly suggests that abnormal glucuronidation of bilirubin and some other aglycones in homozygous Gunn rats is due to genetic abnormalities involving the enzyme(s) itself.

Aminopyrine↗
PubMed1986

Mechanisms of vitamin deficiencies in alcoholism.

Chronic alcoholic patients are frequently deficient in one or more vitamins. The deficiencies commonly involve folate, vitamin B6, thiamine, and vitamin A. Although inadequate dietary intake is a major cause of the vitamin deficiency, other possible mechanisms may also be involved. Alcoholism can affect the absorption, storage, metabolism, and activation of many of these vitamins. Possible factors which cause alterations in the absorption, storage, and metabolism of these vitamins are discussed. Suggestions for management of vitamin deficiencies in chronic alcoholics are also discussed.

Alcoholism↗
PubMed1986

Rapid ethanol elimination in patients with type I glycogen storage disease is an adaptive change resulting from recurrent hypoglycemia.

Patients with deficient activity of hepatic glucose-6-phosphatase (glycogen storage disease type I [GSD-I]) have fasting-induced hypoglycemia, lactic acidemia, hyperuricemia, hyperlipidemia, and a markedly increased capacity for ethanol elimination. The mechanism(s) responsible for the rapid ethanol elimination is not known but has been thought to be directly related to the enzyme defect. We postulated however, that the increased elimination of ethanol was an adaptive phenomenon that would revert toward normal with correction of other blood abnormalities by long-term maintenance of normal blood glucose concentration. Six patients were observed before treatment (group A), and four of the six were observed again 3 to 6 months after dietary treatment had normalized all blood abnormalities (group B). Patients received 16 ml/m2 absolute ethanol as a 5% solution in 0.9% sodium chloride over a 20-minute period. The rate of ethanol elimination was significantly greater (P less than 0.03) in group A than in group B (55.1 +/- 11.1 vs. 37.5 +/- 8.6 mg/dl/hr). Changes in lactate level after ethanol were also significant between the two groups (P less than 0.005). Group A showed a decrease from 9.4 +/- 0.5 to 6.4 +/- 0.4 mEq/L, whereas group B showed an increase in lactate level from 2.7 +/- 0.2 to 4.4 +/- 0.64 mEq/L. Ethanol induced no significant change in blood glucose concentration in group A, whereas there was a significant increase (P less than 0.03) in group B from 93 +/- 6 to 123 +/- 9 mg/dl.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1984

Alcohol interactions with benzodiazepines and cocaine.

A rational management of alcoholic patients requires an understanding of alcohol interactions with other drugs. In this discussion, the influence of alcohol on benzodiazepine and cocaine metabolism is examined. The effect of alcohol may be indirect by producing liver disease and secondary impairment of drug metabolism, or direct following acute or chronic alcohol administration. The acute administration of alcohol suppresses the oxidative metabolism of chlordiazepoxide and diazepam and their principal metabolites. This finding may account partly for the enhanced psychomotor impairment following combined benzodiazepine-alcohol ingestion. The conjugation of lorazepam is also decreased, but for unclear reasons that of oxazepam remains normal. Data are insufficient to establish the effect of chronic alcohol administration on benzodiazepine disposition, especially in man. On the other hand, with respect to cocaine, chronic alcohol exposure causes induction of hepatic microsomal enzyme activity and enhances the production of metabolites that prove injurious to the liver, thereby augmenting the hepatotoxic effect of alcohol.

Alcoholic Intoxication↗
PubMed1983

Hypernatremia and lactulose therapy.

Lactulose is used in the treatment of portal-systemic encephalopathy. Although it is usually safe, a case of hypernatremia has been reported. To evaluate further the association of lactulose therapy and hypernatremia, records of patients with hepatic failure treated with lactulose for encephalopathy were analyzed. In 20 of 75 courses of lactulose treatment, serum sodium level exceeded 145 mEq/L. Mortality was 41% in patients in whom hypernatremia developed as compared with 14% in those who remained normonatremic. In persons who died, hypernatremia persisted; in patients who eventually recovered, the serum sodium level returned to normal. The precise mechanism of hypernatremia in these cases is not clearly defined. As an osmotic cathartic, however, lactulose may cause fecal water loss in excess of sodium, resulting in contraction of extracellular fluid volume and, therefore, hypernatremia.

Creatinine↗
PubMed1983

Inhibition of caffeine elimination by short-term ethanol administration.

Short-term ethanol ingestion has been shown to inhibit the metabolism of a number of drugs metabolized by cytochrome P-450 in both man and laboratory animals. However, the effects of short-term ethanol administration on the metabolism of cytochrome P-448-dependent drugs in man is unknown. Caffeine is a commonly used drug that is metabolized predominantly by a component of the hepatic microsomal mixed-function oxidase complex, known as cytochrome P-448. Therefore the elimination of caffeine given orally was studied in normal volunteers after receiving either orange juice or 0.8 gm/kg ethanol as a 25% solution in orange juice. Short-term administration of ethanol resulted in a significant decrease in the plasma clearance of caffeine from 96.6 +/- 13.4 ml/min to 60.7 +/- 10.5 (mean +/- S.E., p less than 0.05). There was also a corresponding significant increase in the elimination half-life of caffeine from 4.03 +/- 0.52 hr to 6.04 + 0.73 (mean + S.E., p less than 0.01). To determine whether the decrease in caffeine elimination was due to an inhibition of caffeine metabolism by ethanol or to an effect on caffeine absorption, caffeine disposition was studied in four healthy, mongrel dogs after intravenous administration. Each animal served as its own control. Caffeine clearance decreased significantly from a baseline value of 19.6 +/- 1.5 ml/min to 8.0 +/- 1.5 (mean +/- S.E., p less than 0.05) after administration of 3.0 gm/kg ethanol given orally 1 hr before intravenous caffeine injection. These results imply that short-term administration of ethanol inhibits the metabolism of caffeine, a predominantly cytochrome P-448-dependent substrate, in both man and dogs.

Adult↗
PubMed1982

Dual system of intestinal thiamine transport in humans.

The transport of thiamine across the intestine has been characterized in rats but has not been adequately studied in humans. To determine the kinetics of thiamine intestinal transport directly in humans, mucosal tissues were obtained during routine endoscopy from normal-appearing sites at the second portion of the duodenum. With 3H-dextran as the marker of adherent volume, the uptake of 14C-thiamine hydrochloride by the excised mucosa was measured in vitro. By this method thiamine uptake was linear with tissue weight and with incubation time up to 5 min. Results showed that at low thiamine concentrations (0.2 to 2.0 microM), uptake was saturable whereas at high concentrations (5 to 50 microM), uptake was linear with thiamine concentrations. Pyrithiamine, anoxia, N-ethylmaleimide, and replacement of sodium chloride by mannitol reduced the uptake of 0.5 microM thiamine by 42%, 37%, 32% and 35%, respectively (p less than 0.05) but had no effect on the uptake of 20 microM thiamine. These data suggest that, as in the rat, the intestinal transport of thiamine in humans proceeds by a coexistent dual system. At physiologic concentrations, thiamine is transported primarily by an energy-requiring, sodium-dependent active process, whereas at higher pharmacologic concentrations thiamine uptake is predominantly a passive process.

Biological Transport, Active↗