Srikumaran Melethil

Dose-dependent absorption and excretion of vitamin C in humans

Abstract Four subjects ingested 500, 1000 and 2000 mg of ascorbic acid daily for one week according to a three-way crossover design. Following the last dose, serial urine and plasma samples were obtained over a 12-h period. The ascorbic acid content of these samples were determined by an HPLC method employing electrochemical detection. The plasma concentration-time profiles are similar at all 3 doses, with the area under the curve values (mean ± S.D.) being 206.0 ± 50.5, 212.1 ± 40.7, and 231.8 ± 52.6 mg · h/1 for the 500, 1000 and 2000 mg doses. The corresponding percents (mean ± S.D.) of dose recovered in urine are 73.2 ± 25.7, 46.9 ± 21.7 and35.8 ± 12.4. This decrease in recovery is significantly different ( P

Increased blood-brain barrier permeability of amino acids in chronic hypertension

A previous communication from this laboratory reported that brain uptake of libenzapril, a small polar molecule, was enhanced in chronic hypertension (1). The objective of this investigation was to determine if this was a more generalized phenomenon. Therefore, experiments were undertaken to examine the effect of chronic hypertension on the brain uptake of tryptophan (an amino acid with high brain permeability) and glutamic acid (one with low permeability). Brain concentrations of these two amino acids were 5- to 12-fold greater in chronic hypertensive rats, as compared to normotensive rats; the corresponding brain uptake index (BUI) values were 2- to 5-fold higher in the former group. Since blood-brain barrier transport of amino acids involve both saturable (carrier) and non-saturable (most likely, diffusion via pores) mechanisms, data from this study show that hypertension can enhance BBB transport of amino acids by affecting one or both of these pathways.

Aluminum-induced acute cholinergic neurotoxicity in rat.

In the present study the acute effect of intravenous aluminum chloride (1 mg/kg) on choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities of rats was investigated. Aluminum was found to cross the blood-brain barrier (BBB) as indicated by the detection of aluminum in the cerebrospinal fluid (CSF) 30 min after femoral vein injection. Two hours following aluminum injection, ChAT activity in the basal forebrain and hippocampus was significantly reduced by 30% and 22%, respectively, whereas no change was observed in the caudate nuclei. On the other hand, AChE activity was significantly increased by 45% in the caudate nuclei, whereas little change was observed in other brain areas. This report demonstrates that rapid transport of Al across the BBB, and the acute nature of Al neurotoxicity in rats.

Elevation of Serum Aluminum in Humans on a Two-Day Sucralfate Regimen

Serum aluminum concentrations were determined in ten healthy subjects treated with phenytoin 500 mg and with sucralfate and phenytoin in a crossover fashion. Each subject received four 1,000‐mg sucralfate tablets between 8 am and 10 pm one day before the study, and this was repeated during the study day. A total of eight doses of sucralfate was administered over the two‐day period. Serum samples were drawn at 0, 2, 4, 8, 12, 24, 32, and 48 hours after administration. The areas under the serum aluminum concentration‐time curves before and after sucralfate (mean ± SD) were 496.0 ± 80.9 and 770.9 ± 146.6 hr‐ng/mL, respectively. This increase is statistically significant (P < .01), indicating that serum aluminum levels are elevated even after two days of treatment with sucralfate. The results from this study are not in agreement with the only other report on this subject.

Effect of Chronic Hypertension on the Blood–Brain Barrier Permeability of Libenzapril

AbstractVery little information is available on the permeability of theblood–brain barrier (BBB) to small polar drugs inchronic hypertension. The blood and cerebrospinal fluid (CSF)pharmacokinetics of liben-zapril (LZP), a potentangiotensin converting enzyme inhibitor, were investigated inhypertensive (SH) and normotensive (SD) rats.Following intravenous bolus administration of this hydrophilic drug, theterminal rate constant for elimination (β),steady-state volume of distribution (

Liquid chromatographic assay for promethazine in plasma using electrochemical detection

V_{d_{ss} }

Patent issues in drug development: Perspectives of a pharmaceutical scientist-attorney

), and systemic clearance (CL) were similar in these two animalgroups. Other pharmacokinetic parameters (Cp°,α, kl2, and k21)were significantly (P < 0.05) greater in thehypertensive group, except for the volume of the central compartment(Vc) and ratio of Vc to