RAPID ABSORPTION FROM THE URINARY BLADDER OF A SERIES OF n‐ALKYL CARBAMATES: A ROUTE FOR THE RECIRCULATION OF DRUGS

Abstract

I The rate of loss of a series of n-alkyl carbamates from the lumen of the urinary bladders of female rats has been studied. 2 The rate of loss obeys first order kinetics and was not affected by water flux across the bladder wall nor by binding of the carbamates to it. 3 The rate of loss of octyl carbamate was reduced by about 76% by the presence of 5% Tween 80. Histological evidence indicates that this may be due to the formation of a thin luminal lining which may be adsorbed Tween 80 or mucopolysaccharide material. 4 The absorption rate of the carbamates was limited by their hydrophilicity but reached a plateau for the more lipophilic homologues with a half life for loss of approximately 10 min. 5 The implications of these results with regard to the recirculation of unmetabolized drugs and hydrolysed conjugates of drugs, the systemic absorption of intravesically applied cancer chemotherapeutic agents and bladder wall permeability to carcinogens are discussed.

Diagnosis of bladder carcinoma using protoporphyrin IX fluorescence induced by 5‐aminolaevulinic acid

“…However, 88% of well differentiated G1 tumours and 67% of mild dysplastic lesions in the present study showed PPIX fluorescence, which either contradicts the results of Fellows et al [9] or indicates that in addition to diffusion that there is an active mechanism for ALA transport into the cell, suggesting that there are indeed differences in the ALA/PPIX‐metabolism between normal and dedifferentiated cells. The existence of an active transport mechanism is supported by animal studies, which have shown that substances with biochemical properties similar to ALA (molecular weight <200, water soluble and yet sufficiently lipophilic for binding with plasma membranes) can be absorbed by the urothelium [13–15]. After instillation of amino acids and glucose, a concentration gradient from the mucosa to serosal surfaces has been detected [13,14].…”

Aminolevulinic Acid Derivatives and Liposome Delivery as Strategies for Improving 5-Aminolevulinic Acid- Mediated Photodynamic Therapy

“…Systematic studies [77] with a series of homologue carbamates have shown a relative constant absorption rate from the urinary bladder for compounds with log P (apparent partition coefficients between octanol and PBS) values ranging between 0.8 and 2.8, while carbamates with log P values less than 0.8 have shown reduced bladder-wall absorption. Uehlinger and collaborators [17] determined that the log P value for ALA and Me-ALA (1) were negative, whereas for ethyl-ALA (2) was 0.8, butyl-(3) 1.4, hexyl-(15) 1.8 and octyl-2.6, which suggests a higher bladder uptake for ALA esters containing two or more carbon atoms in their ester function.…”

Photodetection of early human bladder cancer based on the fluorescence of 5-aminolaevulinic acid hexylester-induced protoporphyrin IX: a pilot study

“…Consequently, in order to increase the transport across cellular membranes, fairly high drug doses and increased administration times have to be used. This deficiency results in a low penetration depth (Warloe et al, 1992;Loh et al, 1993;Peng et al, 1995) and an ALA-induced PpIX distribution, which is not optimized for the PDT of the deep layers of nodular lesions in the urothelium (Iinuma et al, 1995;Chang et al, 1996) after topical ALA application.Systematic studies have shown that the modification of a drug to an ester, an amide or a urethane by the addition of a long-chain hydrocarbon improves penetration through biological barriers (Bridges et al, 1979;Jain, 1987aJain, , 1987b. After penetration into the cell, the ester derivative can then, for example, be hydrolysed back to the free ALA by non-specific esterases.…”

“…Systematic studies have shown that the modification of a drug to an ester, an amide or a urethane by the addition of a long-chain hydrocarbon improves penetration through biological barriers (Bridges et al, 1979;Jain, 1987aJain, , 1987b. After penetration into the cell, the ester derivative can then, for example, be hydrolysed back to the free ALA by non-specific esterases.…”