Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report two cases of herpes-zoster in which the administration of acyclovir to patients with end-stage renal failure treated by continuous ambulatory peritoneal dialysis (CAPD) resulted in acyclovir neurotoxicity, even though the doses administered were within those recommended by the manufacturer's data sheet for patients with renal failure. Acyclovir removal was negligible with peritoneal dialysis and one patient died. The other patient was successfully treated with hemodialysis, which effectively reduced plasma concentrations, resulting in an improvement in conscious state. Acyclovir neurotoxicity should be considered in patients with renal failure who have been treated for viral infections, in whom the conscious state has deteriorated despite normal brain computed tomography (CT) scan and lumbar puncture investigations. Hemodialysis is the preferred treatment for the rapid removal of acyclovir.
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PMID:Neurotoxicity of acyclovir in patients with end-stage renal failure treated with continuous ambulatory peritoneal dialysis. 146 97

Acyclovir is an effective agent for the treatment of herpes virus infections, however, the pharmacokinetics of the drug are altered in renal failure. We studied this drug in a continuous ambulatory peritoneal dialysis (CAPD) patient who was immunocompromised and had cutaneous herpes infection. The elimination half-life (17.1 hours) was similar to that reported for end-stage renal disease (ESRD) patients, while the volume of the central compartment (29.6 L/1.73 m2), the steady state volume of distribution (68.1 L/1.73 m2), and the total body clearance (48.3 mL/min/1.73 m2) were greater. The mean CAPD clearance was only 4.4 mL/min, with less than 10% of an administered dose being recovered in the 24-hour dialysate. Further studies are needed to establish a dosing regimen for CAPD patients.
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PMID:Acyclovir pharmacokinetics in a patient on continuous ambulatory peritoneal dialysis. 371 58

Acyclovir (Zovirax) is a highly specific antiherpes virus agent. Extensive investigations of the pharmacokinetics in man have shown it to have a useful half-life of about three hours and to be largely excreted unchanged in the urine. Crystaluria can be avoided provided the patient is well hydrated and attention is paid to the dosing instructions especially in patients with renal failure. In vitro ED50s (the drug concentration inhibiting virus replication by 50%) bear some general relevance to effective plasma levels in man. A new prodrug of acyclovir, 2-amino-9-[2-hydroxyethoxy methyl]-9H-purine (A515U), which is converted to acyclovir by xanthine oxidase is rapidly absorbed from the human gut and converted to acyclovir. This prodrug provides the opportunity to design regimes that are more convenient for the patient and may be more effective than acyclovir itself in the therapy of the less sensitive herpes viruses (e.g. Epstein-Barr virus and the Cytomegalovirus).
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PMID:The clinical pharmacology of acyclovir and its prodrugs. 386 24

Acyclovir is a new antiviral drug that acts as a specific inhibitor of herpesvirus DNA polymerase. It shows good in vitro activity against herpes simplex and varicella-zoster viruses. The drug may be administered topically to the skin, intravenously, orally, or topically to the eye (only topical and intravenous preparations are currently available). Acyclovir kinetics are described by a two-compartment open model. The drug and its metabolites are excreted by the kidney via glomerular filtration and tubular secretion. Dosage adjustment is required in patients with renal failure. Safety and tolerance studies in animals and humans have shown acyclovir to be very well tolerated. The most important adverse effect is crystalluria and elevated serum creatinine related to bolus intravenous administration. Other reported adverse effects include infusion site inflammation and rash. Topical acyclovir is effective for treating initial genital herpes and mucocutaneous herpes in the compromised host, but has not been shown to be clinically useful for recurrent labial or genital herpes. Intravenous acyclovir is effective for mucocutaneous herpes infections in the compromised host and initial genital herpes in the normal host; it is being evaluated for the treatment of herpes simplex virus encephalitis and varicella-zoster infections. An investigational oral preparation may prove to be effective therapy for both initial and recurrent genital herpes. Acyclovir therapy does not eliminate latent virus or prevent subsequent recurrences.
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PMID:Acyclovir: mechanism of action, pharmacokinetics, safety and clinical applications. 635 82

Acyclovir (ACV) is almost entirely eliminated by the kidneys and has a terminal plasma half-life (t1/2) of 2 to 3 hr in subjects with normal renal function. To determine the drug's kinetics and tolerance in patients with severe renal failure, six anuric subjects on long-term hemodialysis were studied. Each received a 1-hr infusion of 2.5 mg/kg IV ACV. The kinetics are well described by a two-compartment open model. ACV terminal plasma t 1/2 and the total body clearance were 19.5 +/- 5.9 hr (mean +/- SD) and 28.6 +/- 9.5 ml/min/1.73 m2. Peak (end of infusion) and 8- and 24-hr plasma ACV concentrations were 37.5 +/- 23.3, 10.3 +/- 2.9, and 6.4 +/- 2.4 microM. Approximately 48 hr after the start of the infusion the subjects were hemodialyzed for 6 hr. The pre- and posthemodialysis ACV plasma levels were 2.74 +/- 1.38 and 1.11 +/- 0.60 microM. The terminal ACV t1/2 during hemodialysis was 5.7 +/- 0.85 hr. During hemodialysis paired arterial and venous samples showed that ACV was readily dialyzed, with a mean coefficient of extraction of 0.45 +/- 0.12. The dialysis clearance of acyclovir was 81.8 +/- 12.6 ml/min. None of the patients had any ACV-related adverse effects. Since ACV elimination is markedly reduced in end-stage renal failure and because ACV is readily hemodialyzible, dosage modification are needed to avoid cumulation and to replace dialyzed drug.
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PMID:Acyclovir kinetics in end-stage renal disease. 707 9

A 9-year-old boy developed acute renal failure following intravenous acyclovir (30 mg/kg per day) administered for 6 days to treat herpetic encephalitis. Physical findings and urine output were normal, except for increasing blood urea nitrogen (BUN), serum creatinine and mild proteinuria. Acyclovir was discontinued. However BUN and serum creatinine continued to increase and peaked on the following day at 8.6 mmol/l of urea (24 mg/dl) and 194 mumol/l (2.2 mg/ml), respectively. Conservative treatment and hydration were carried out. The kidney function returned to normal within 1 week. The use of acyclovir when necessary in renal failure patients is discussed.
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PMID:Acute renal failure in a child associated with acyclovir. 763 29

A 69-year-old man developed confusion and disorientation, following intravenous administration of acyclovir for herpes zoster at the right C5 area. His consciousness was disturbed four days after the beginning of acyclovir therapy (daily dose: 500 mg, every 12 h), and the symptoms resolved two days after cessation of acyclovir. Neuroradiological examination revealed no intracranial abnormality, and the routine CSF examination was within the normal range of values except for a mild elevation of IgG (7.4 mg/dl). An electroencephalogram showed diffuse slow activities without paroxysmal waves on admission, but the findings of electroencephalograms were gradually normalized in parallel with the recovery of consciousness. Fever, signs of meningeal irritation, involuntary movement or renal dysfunction were not observed during the course of illness. Although the serum concentration of acyclovir was not elevated, we considered the adverse effects of acyclovir had resulted in his consciousness disturbance. Acyclovir is greatly useful for herpes simplex and varicella-zoster virus infections, and its complications are extremely rare. However, several reports described various neuropsychiatric side effects in patients receiving acyclovir. Most of such cases had an association with severe renal failure or malignant tumor; actually, an intense malignancy surveillance over our case revealed thyrogenic papillary adenocarcinoma without metastasis. The excretion of acyclovir is mainly through the kidney, so that the neurotoxicity of acyclovir in cases with renal insufficiency stems from its excessive accumulation in the body. In malignancy complicated patients, on the other hand, some authors surmised about the influences from the co-use of other neurotoxic drugs or radiation therapy, but reasons for such conditions remain obscure. The neuropsychiatric manifestation caused by acyclovir is an entity distinguishable from viral encephalitis, and a careful surveillance for malignancy is required in such cases.
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PMID:[A patient with thyroid carcinoma who developed consciousness disturbance during acyclovir administration for herpes zoster]. 881 Aug 56

A 5-year-old girl with a kidney transplant developed post-transplant Epstein-Barr virus-induced lymphoproliferative disease. She was treated with acyclovir, alpha-interferon, and gamma globulin. A transplant nephrectomy was performed on day 4 due to acute rejection and she was started on hemodialysis. The acyclovir dose was decreased at this time. However, 6 days following the start of acyclovir she developed progressively worsening neurological symptoms resulting in a coma on day 8. Fourteen days after acyclovir was begun pre- and post-dose serum concentrations were 7.02 microM and 182.5 microM, respectively. Acyclovir was then discontinued and 2 days later the child's neurological status began to improve. We conclude that acyclovir in children with end-stage renal failure may lead to severe and reversible neurotoxicity, despite acyclovir dosage adjustment based on renal impairment.
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PMID:Acute acyclovir neurotoxicity in a hemodialyzed child. 943 56

We present a critically ill patient with severe renal failure and anuria who underwent hemodialysis (HD), continuous veno-venous hemodialysis (CVVHD) and continuous veno-venous hemodiafiltration (CVVHDF) at different occasions, with 2 commonly used high-efficiency dialyzers (F-8 and CA-210), while receiving i.v. acyclovir. We estimate that during 24 hours of CVVHD with F-8 dialyzer approximately 18% and during 24 hours of CVVHDF with CA-210 dialyzer approximately 65% of the daily administered acyclovir is removed. This is comparable to the amount removed during 4 6 hours of HD, as reported previously. The percentage acyclovir extraction was 84% and 60% during CVVHD and CVVHDF with F-8 and CA-210 dialyzers, respectively. Acyclovir clearance during CVVHD was 14 ml/min and during CVVHDF was 17 ml/min, with F-8 and CA-210 dialyzers, respectively. Acyclovir half-life was 22.5 and 25.5 hours in 2 occasions off any type of renal replacement therapy, and it was 19.5 hours during CVVHDF with CA-210 dialyzer.
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PMID:Removal of acyclovir during continuous veno-venous hemodialysis and hemodiafiltration with high-efficiency membranes. 1107 13

In continuous ambulatory peritoneal dialysis (CAPD) patients, acyclovir-induced neurotoxicity is reported to be associated with high serum drug levels even when following the recommended reduced doses for this renal failure population. In view of the high oral bioavailability of valaciclovir (the L-valyl ester of acyclovir) the risk of neurotoxicity becomes more prominent. The present study was conducted in 12 CAPD patients who were administered a single oral dose of 500 mg valaciclovir. Acyclovir was analyzed by high-performance liquid chromatography. Relative pharmacokinetic parameters were estimated based on acyclovir concentrations at 8, 12 and 24 h post-dose. High inter-patient variations were observed with acyclovir apparent total clearance 7.238 +/- 4 l/h and half-life (T1/2) 22.27 +/- 16.82 h. However, dosage simulations confirmed supratherapeutic acyclovir concentrations for all participants when following the recommended dose of 1,000 mg valaciclovir/24 h for varicella zoster infections.
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PMID:Evaluation of valaciclovir dosage reduction in continuous ambulatory peritoneal dialysis patients. 1202 36


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