PubMed Health⌕ Search

Biomedical subjects

G Plante

Publications and source records attributed to G Plante.

18 recordsLinked to original sources

Bioequivalence of abacavir generic and innovator formulations under fasting and fed conditions.

OBJECTIVE: Abacavir sulfate is a synthetic carbocyclic nucleoside analogue indicated for the treatment of HIV-1 infection in combination with other antiretroviral agents. The objective of the current study was to determine the bioequivalence between a generic formulation of abacavir and the innovator product. MATERIAL AND METHODS: A total of 80 subjects were randomly assigned to receive a single 300 mg oral dose of abacavir sulfate as the generic (Ranbaxy-Abacavir, Ranbaxy Laboratories Ltd., equivalent to 300 mg of abacavir) and innovator (Ziagen, GlaxoSmithKline) tablet formulations in 2-way crossover studies performed under fasting (n=40) and fed (n=40) conditions. Multiple blood samples were collected over 14 hours and plasma concentrations of abacavir were assayed using an LC/MS/MS method with a limit of quantitation of 25.0 ng/ml. Pharmacokinetic (PK) parameters were calculated using noncompartmental methods. RESULTS: Under fasting conditions, geometric mean area under the curve from time 0 to the last measurable concentration (AUC(0-t)), area under the curve extrapolated to infinity (AUC(0-infinity) and maximum plasma concentrations (Cmax) of abacavir for the generic (5565 ng x h/ml, 5668 ng x h/ml and 2526 ng/ml, respectively) and innovator (5675 ng x h/ml, 5770 ng x h/ml and 2528 ng/ml, respectively) products were very similar. Under fed conditions, mean values of AUC(0-t) AUC(0-infinity) and Cmax for the generic (4487 ng x h/ml, 4571 ng x h/ml and 1841 ng/ml, respectively) and innovator (4574 ng x h/ml, 4654 ng x h/ml and 1781 ng/ml, respectively) formulations were also very similar. Ratios of LSM and 90% confidence intervals of PK parameters between the 2 formulations were within 80.0 - 125.0% under fasting and fed conditions, suggesting that the 2 tablet formulations resulted in similar rate and extent of bioavailability. Adverse events for the generic and innovator products were similar in nature and frequency in the fasting and fed studies. CONCLUSIONS Based on the above results, the generic tablet formulation of abacavir developed by Ranbaxy should be equally effective as the innovator product.

Adult↗

Identification of proximal tubule segments in the mouse nephron by simultaneous visualization of alkaline phosphatase and gamma-glutamyl transpeptidase.

ALP and gamma-GT are 2 brush border enzymes that can be individually demonstrated on adjacent sections by the histochemical methods of Mayahara (ALP) and Rutenberg (gamma-GT). On the basis of each enzyme activity, it was possible to recognize different categories of tubules in the mouse nephron. In fact, both enzymes were heterogeneously distributed along the proximal tubule, but in opposite gradients. The various staining intensities probably corresponded to proximal segmentation, but were sometimes difficult to evaluate. A technique was perfected to localize both enzymes in the same tissue section. Since each enzyme produced a distinct type of colored precipitates (ALP: black, gamma-GT: red), 4 categories of tubules could be identified, according to staining characteristics: 1. black tubules where ALP activity was predominant, corresponded to S1 segments, 2. black and red tubules where the 2 activities were about equivalent, were considered as parts of S2, 3. red ones where gamma-GT activity was high, were identified as portions of S3, 4. negative tubules where no activity was apparent, represented distal and straight collecting tubules. In addition to economize time and tissue, this simple technique permits to easily estimate variations in enzyme activities that probably correspond to structural and functional differences in the segments of the proximal tubule.

Alkaline Phosphatase↗

Heterogeneous distribution of alkaline phosphatase and gamma-glutamyl transpeptidase in the mouse nephron.

In the mouse nephron, ALP and gamma-GT were found to be heterogeneously distributed along the proximal tubule. For both enzymes, 4 large categories of tubules could be recognized on the basis of the enzymatic activity: intense; intermediate; weak; negative. The localization of ALP and gamma-GT was in opposite gradient along the proximal tubule and it apparently corresponded to the 3 sequential segments S1, S2, and S3. In fact, S1 could be identified with certainty because this first portion was often seen attached to the renal corpuscle. This segment displayed a very intense ALP activity (category 1), but a weak one for gamma-GT (category 3). Intermediate tubules for ALP and gamma-GT activities (category 2) seemingly were parts of S2. Those tubules where ALP activity was weak (category 3) while that of gamma-GT was intense (category 1) probably belonged to S3. As a result, it becomes possible to clearly distinguish the segments S1, S2, and S3, not only on a structural and biochemical basis but as well by the localization of brush border enzymes. Distal tubules showed no enzyme activity (category 4). In other respects, the presence of ALP and gamma-GT on the parietal layer of Bowman's capsule strongly suggests that these tall cylindrical cells are morphologically and enzymatically identical to those of the S1 segment, and that they might have similar functional roles.

Alkaline Phosphatase↗

Simultaneous visualization of alkaline phosphatase and gamma-glutamyl transpeptidase in kidney sections.

An histochemical method is presented to simultaneously localize, for the first time, alkaline phosphatase (ALP) and gamma-glutamyltranspeptidase (gamma-GT) in the kidney. The reaction product of ALP activity appears as a dark brown precipitate of lead sulfide, while a bright red copper chelate of an azo dye (Fast blue BBN salt) final product indicates sites of gamma-GT activity. The amalgamation of Mayahara's (ALP) and Rutenberg's (gamma-GT) techniques resulted in the demonstration of various categories of kidney tubules, according to the staining reaction of the cell brush borders: Black tubules where ALP predominates; Intermediate tubules showing a mixture of brown and red precipitates; Red tubules indicating a prevalence of gamma-GT activity; Negative tubules. A possible relation might exist between the staining characteristics observed and the different proximal tubule segments, thus allowing their distinction. In addition, this technique has the advantage to permit the concomitant study of ALP and gamma-GT distribution on the same tissue section instead of serial sections, so reducing the number of manipulations and observations as well as the amount of tissue required.

Alkaline Phosphatase↗

Presence of alkaline phosphatase and gamma-glutamyl transpeptidase on the parietal layer of Bowman's capsule.

Generally, the parietal layer of Bowman's capsule in the mammal kidney consists of a squamous epithelium resting upon a basement lamina. However, tall cylindrical cells resembling those of the proximal tubules were observed on the outer wall of Bowman's capsule in the mouse and rat kidneys. These cells were provided with an apical brush border and were positive for alkaline phosphatase and gamma-glutamyl transpeptidase suggesting phosphate and amino acid transport at the capsular level.

Alkaline Phosphatase↗

Patterns of change in selected serum chemical parameters of middle and later years.

Six serum constituents known to vary with renal function were analyzed in a probability sample of 500 persons 55 years and over, and their sex trends compared to other ages. Creatinine, BUN and alkaline phosphatase are elevated in this group whereas calcium is low and phosphorus strikingly so, especially in males. A possible explanation lies in age-related renal parenchymal changes which influence both glomerular filtration and tubular functions in ways that differ from true renal disease. These results have directed implications for geriatric diagnosis and therapy.

Age Factors↗

[Child psychitary].

Explore the source record for details and available documents.

Child Behavior Disorders↗