Uptake of glycine froml-alanylglycine into renal brush border vesicles

Welch, Charles L.; Campbell, Benedict J.

doi:10.1007/bf01875375

Cited by 29 publications

(11 citation statements)

References 43 publications

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“…Welch and Campbell (14) suggested that the enzyme might play a role in retaining essential amino acids by hydrolyzing filtered dipeptides that would otherwise be excreted in the urine. The effects of enzyme inhibition by cilastatin on neonatal homeostasis are unknown.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of imipenem-cilastatin in neonates

Freij¹,

McCracken²,

Olsen³

et al. 1985

Antimicrob Agents Chemother

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Imipenem and its renal dehydropeptidase I inhibitor, cilastatin, were coadministered intravenously in a 1:1 ratio to 30 newborns. Five infants each received single doses of 10, 15, or 20 mg/kg of both drugs. Concentrations in plasma were proportional to the administered dose, and cilastatin achieved consistently higher concentrations than did equivalent doses of imipenem because of its smaller volume of distribution. The pharmacokinetics of both drugs were best described by a one-compartment model. The plasma half-lives of imipenem were 1.7 to 2.4 h, whereas those of cilastatin were 3.9 to 6.3 h. The plasma clearance of cilastatin was approximately one-quarter Imipenem is a beta-lactam antibiotic with a carbapenem nucleus (5). It has excellent activity against aerobic and anaerobic gram-positive and gram-negative bacteria (1,4,8,13). Cilastatin (MK0791) is an inhibitor of dehydropeptidase I, the renal tubular brush border enzyme that inactivates imipenem (9). The coadministration of imipenem and cilastatin increases the urinary recovery of imipenem and, to a lesser extent, its concentration in plasma (9). In experimental animals, the combination appears to prevent the nephrotoxicity associated with the administration of imipenem alone (3).By virtue of its high in vitro potency against Escherichia coli, streptococci, Staphylococcus aureus, Listeria monocytogenes, Pseudomonas aeruginosa, and enterococci (1,2,4,8), imipenem potentially might be the most useful single agent for initial, empirical treatment of neonatal infections. Imipenem provides broader coverage than the standard ampicillin-plus-aminoglycoside regimen while reducing the potential toxicities of antibiotic combinations to the newborn.This study was undertaken to determine the pharmacokinetic properties of both imipenem and cilastatin (primaxin) in neonates. MATERIALS AND METHODSStudy patients. The study population consisted of 30 newborn infants born at Parkland Memorial Hospital, Dallas, Tex., who were being treated with ampicillin and gentamicin for suspected sepsis (Table 1). After informed, written consent was obtained from the parents, one to eight doses of imipenem-cilastatin (in a 1:1 ratio) were administered intravenously. Complete blood counts were obtained at the start of the study and again after the last dose of imipenem-cilastatin was infused. Serum creatinine, urinalysis, and other laboratory studies were performed as required by the condition of the patients.The infusion solutions were prepared by mixing equal amounts (in milligrams) of imipenem (powder form) and * Corresponding author. cilastatin (liquid form) and then diluting the resulting slurry in sufficient sterile saline to achieve a final concentration of 5 mg/ml for both drugs. The consistency of this preparation method was evaluated by measuring the concentrations of both imipenem and cilastatin in specimens from seven different infusion solutions.A single dose of imipenem-cilastatin was infused intravenously over 60 min in 15 newborns; five each received doses of 10, 15, ...

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of imipenem-cilastatin in neonates

Freij¹,

McCracken²,

Olsen³

et al. 1985

Antimicrob Agents Chemother

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“…MDP has been implicated in the metabolism of Cys-Gly and the X-CG, leukotriene D 4 (LTD 4 ) (Adachi et al, 1989). The enzyme is found in the renal brush border microvillar membrane and also in the lung (Brewis et al, 1994;Campbell et al, 1990;Curthoys et al, 1980;Welch and Campbell, 1980). In pig kidney, immunohistochemical analysis revealed that MDP is present in the cortex but not in the medulla (Littlewood et al, 1989).…”

Section: Cys-gly Conjugate Hydrolysismentioning

confidence: 99%

Hydrolysis of S-aryl-cysteinylglycine conjugates catalyzed by porcine kidney cortex membrane dipeptidase

Poon

Josephy

2012

Xenobiotica

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“…RDPase is a zinc-metalloenzyme principally localized in the brushborder of the renal proximal tubule (Welch and Campbell, 1980), but is also found with high activity in other tissues such as the lung, pancreas, testis and intestinal mucosa (Campbell et al, 1990;Kera et al, 1999). Dipeptidase activity was also detected in the urine of human, where it was named as urinary dipeptidase (Udpase), and was subsequently purified from human urine (Park et al, 1992).…”

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confidence: 99%

“…RDPase and Udpase were identified as the same enzyme on the basis of various physicochemical characteristics such as substrate specificity, immunoreactivity and amino acid sequence identity (We et al, 1997). Various physiological role of this enzyme has been suggested such as hydrolysis of dipeptides for reabsorption in the kidney (Welch and Campbell, 1980), *To whom correspondence should be addressed. Tel: 82-62-530-2923, Fax: 82-62-530-2949 and metabolism of glutathione and leukotriene D4 (Campbell et al, 1990).…”

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confidence: 99%