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PubMed2006

Anti-filarial activity of novel formulations of albendazole against experimental brugian filariasis.

The study was aimed at developing better orally active albendazole (ALB) formulations. Six formulations (ALB-1 to ALB-6) were prepared and tested against Brugia malayi in Mastomys coucha and jird (Meriones unguiculatus) at 200 mg/kg, orally, for 5 consecutive days. The anti-filarial efficacy was assessed against microfilariae (mf), adult worms and female reproductive potential. Three of the 6 ALB formulations showed greatly improved female worm sterilizing potential (ALB-1: 90%; ALB-3: 63%; ALB-4: 77% of untreated control) in B. malayi - M. coucha model. Sterilization efficacy of ALB-1 was also better than that shown by pure-ALB (P<0.001) or its marketed tablet formulation, Zentel (P<0.01), while that of ALB-4 was better than pure-ALB (P<0.05). The activity of ALB-3, pure-ALB and Zentel was, however, comparable. ALB-1 also showed late microfilaricidal activity with a maximum of 78% fall in microfilarial count. In contrast, neither the pure ALB nor Zentel showed any microfilaricidal activity. In the jird - B. malayi model, ALB-1 and ALB-4 showed marginal sterilizing efficacy whereas pure ALB or Zentel were ineffective. In conclusion the anti-filarial efficacy of ALB-1 was found to be superior to pure-ALB or Zentel.

Albendazole↗
PubMed1984

Albumin absorption and catabolism by isolated perfused proximal convoluted tubules of the rabbit.

Overall characteristics and kinetics of tubular absorption of albumin (Alb) were studied in isolated perfused proximal convoluted tubules of the rabbit. The fate of absorbed Alb was determined in tubules perfused with low [Alb]. Alb was labeled with tritium by reductive methylation ( [3H3C]Alb). At [Alb] = 0.03 mg/ml, approximately 80% of the absorbed [3H3C]Alb was released to the peritubular bathing solution as catabolic products. Transcellular transport of intact [3H3C]Alb was negligible. Iodoacetate (IAA, 4 mM) inhibited albumin absorption (JAlb) by greater than 95% and fluid reabsorption (JV) by 55%. At [Alb] = 0.1 mg/ml the absorption rate of a derivatized cationic Alb (pI = 8.4) was fivefold greater (P less than 0.01) than that of anionic Alb. Higher cationic [Alb] had deleterious effects on tubular functions. Overall Alb absorption was of high capacity and low affinity (JmaxAlb = 3.7 ng/min per mm tubule length, apparent Michaelis constant (Km) = 1.2 mg/ml). A low capacity system that saturates at near physiological loads was also detected (JmaxAlb = 0.064 ng/min per mm, apparent Km = 0.031 mg/ml). High [Alb] did not alter the rate of endocytic vesicle formation as determined by the tubular uptake of [14C]inulin. Results show that Alb absorption is a saturable process that is inhibited by high IAA concentrations and is affected by the charge of the protein. Absorbed Alb is hydrolyzed by tubular cells and catabolic products are readily released to the peritubular side. The dual kinetics of Alb absorption may be due to a combination of adsorptive endocytosis (low capacity system) and fluid endocytosis of albumin aggregates (high capacity system). Results indicate that albuminuria occurs much before albumin absorption is saturated. The kinetic characteristics of the process of tubular absorption of albumin helps to explain the concomitance of albuminuria, increased renal catabolic rates of albumin, and renal cell deposition of protein absorption droplets in severe glomerular proteinurias.

Absorption↗