acyclovir and Liver-Diseases

Neonatal Herpes Simplex Virus (HSV) infection is a serious illness with significant mortality and morbidity for disseminated disease. Clinical diagnosis of neonatal HSV infection is often difficult without evidence of HSV exposure, for example, absence of a rash or the presence of non-specified manifestations in an infant. Early recognition and treatment with high-dose Acyclovir may dramatically improve the short and long-term outcomes. We describe an infant with disseminated disease due to HSV-1 infection, who first presented clinical and radiologic features of pneumonia. The diagnosis was performed post-mortem by Real-Time Polymerase Chain Reaction (PCR) analysis of blood, cerebrospinal fluid and pleural liquid of the infant. Tissue PCR revealed a disseminated HSV-1 infection, with a high viral load detected in liver, lungs, brain, heart, striated muscle, kidneys, and thymus tissues. This case report highlights the need for neonatologists to raise awareness about the different clinical manifestations of disseminated neonatal HSV infection. HSV infections should be prominent in the differential diagnosis of an infant under four weeks of age with fever, pneumonia, unexplained seizures or sepsis-like disease, particularly if unresponsive to antibiotics. Early initiation of appropriate antiviral therapy for high-risk infants undergoing testing for HSV infection can be essential to prevent significant morbidity and mortality.

Topics: Acyclovir; Brain; Diagnosis, Differential; DNA, Viral; Early Diagnosis; Fatal Outcome; Heart; Herpes Simplex; Herpesvirus 1, Human; Humans; Infant, Newborn; Kidney; Liver; Liver Diseases; Lung; Lymphoid Tissue; Male; Muscle, Striated; Organ Specificity; Pneumonia, Viral; Pregnancy Complications, Infectious; Radiography; Real-Time Polymerase Chain Reaction; Viral Load

Acute liver diseases of pregnancy are common and usually transient and reversible. Given the number of different possible diagnoses, performing a large biological screening and a proper iconographic documentation is key. It makes sure no etiology fatal to the mother and her fetus is missed.

Topics: Acyclovir; Adult; Antiviral Agents; Drug Resistance, Microbial; Female; Herpes Simplex; Humans; Liver Diseases; Liver Failure; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third

The antiviral effect of azidothymidine (AZT) can be potentiated by acyclovir (ACV), and this drug association has been used in the management of HIV-infected patients. In the present study we examined the effects of this association on the livers and kidneys of both pregnant rats and their concepts. Previous data from this laboratory suggested that the deleterious effects of ACV on rat pregnancy are due to its extraplacental actions and these are, at least in part, counteracted by concomitant treatment with AZT. Kidneys and livers of pregnant rats were noticed to be much more sensitive to the toxic action of the drugs than those of their concepts, ACV eliciting much more evident morphological alterations than did AZT. Contrary to what was expected, in the group of rats treated with both drugs AZT was not able to diminish the severity of the alterations evoked by ACV. The proposed "protective" action of AZT against the abortive effect of ACV on rat pregnancy does not seem to be exerted through a renal or hepatic pathway.

Topics: Abortion, Spontaneous; Acyclovir; Animals; Antiviral Agents; Chemical and Drug Induced Liver Injury; Drug Synergism; Female; Kidney; Kidney Diseases; Liver; Liver Diseases; Pregnancy; Pregnancy Complications; Rats; Rats, Wistar; Zidovudine

The pharmacokinetic profile of penciclovir was determined after a single 500-mg dose of its oral precursor, famciclovir, in 9 healthy volunteers and in 14 patients with chronic hepatic disease. Plasma and urine samples were analyzed for concentrations of penciclovir and 6-deoxy-penciclovir using a reverse-phase high-performance liquid chromatography (HPLC) method. Famciclovir was not quantifiable in patients with hepatic disease, and 6-deoxy-penciclovir was quantifiable in only a limited number of specimens. The extent of systemic availability of penciclovir, as measured by AUC0-infinity, was similar in patients with hepatic disease and in healthy subjects. In contrast, Cmax was significantly lower (average decrease of 43%) in subjects with hepatic disease relative to healthy normal subjects. Median Tmax for subjects with hepatic disease was significantly increased (by 0.75 hours) compared with subjects with normal liver function. These data suggest a decrease in the rate, but not the extent, of systemic availability of penciclovir in patients with hepatic disease. It should be unnecessary to modify the dose of famciclovir for subjects with compensated hepatic disease and normal renal function.

Topics: 2-Aminopurine; Acyclovir; Administration, Oral; Adolescent; Adult; Biological Availability; Chromatography, High Pressure Liquid; Chronic Disease; Famciclovir; Female; Guanine; Humans; Liver Diseases; Male; Metabolic Clearance Rate; Middle Aged; Prodrugs

To determine the pharmacokinetic parameters of acyclovir disposition in neonates with renal dysfunction.. Prospective sequential open enrollment of neonates with presumed herpes group virus infections.. Neonatal intensive care units in the greater Minneapolis-St. Paul metropolitan area.. Sixteen neonates with gestational ages between 27 and 40 weeks (median 38 weeks) were given acyclovir between days 1 and 56 of life to treat presumed herpes virus infections. Six infants were critically ill with multisystem disease, five infants had hepatic failure and underwent blood exchange transfusion, and five infants had renal failure. A mean of four (range 1 to 19) serum acyclovir concentrations per patient were measured by radioimmunoassay. Pharmacokinetic parameters were calculated from acyclovir concentrations in 46 samples from 16 patients.. The pharmacokinetic disposition of acyclovir was described as a two-compartment model. Although the ranges for acyclovir clearance and terminal elimination (t 1/2 beta) were wide, a statistically significant relationship was demonstrated between clearance and beta versus serum creatinine concentration. The average t 1/2 beta for infants with serum creatinine level less than 1 mg/dl (88 mumol/L) was 5.0 hours, and 15.6 hours for those with serum creatinine level greater than 1 mg/dl.. Neonates with hepatic or renal dysfunction or young premature infants accumulate acyclovir when dosed without adjustment for organ dysfunction. Measurement of serum creatinine or creatinine clearance can be useful in the dosing of acyclovir in neonates.

Topics: Acyclovir; Creatinine; Herpes Simplex; Herpes Zoster; Humans; Infant; Infant, Newborn; Infant, Premature; Kidney Diseases; Liver Diseases; Prospective Studies

Topics: Acyclovir; Agranulocytosis; Antibodies, Viral; Central Nervous System Diseases; Chickenpox; Child; Herpesvirus 3, Human; Humans; Leukopenia; Liver Diseases; Male; Neutropenia