Renal function after acyclovir intravenous injection.

Plasma urea or creatinine was noted to be raised in 58 of 354 patients treated with intravenous acyclovir. This occurred after intravenous bolus injection of high dosages of acyclovir but the risk was considerably reduced by slow intravenous infusion of the same dosage over one hour, with adequate hydration of the patient and adjustment of dosage in patients with preexisting impaired renal function. Animal studies indicate that the impairment of renal function associated with high bolus injections of acyclovir is due to crystal formation in the renal tubules and/or the collecting ducts, and that the crystals are removed after cessation of treatment. The special problems involved in the treatment of patients with herpes encephalitis necessitating limited fluid intake and the possible interaction with other nephrotoxic drugs are discussed.

Acyclovir - a review of the preclinical and early clinical data of a new antiherpes drug.

A review of the literature on acyclovir (Zovirax), a new antiherpes drug, with particular activity against herpes simplex virus types I and II and also against varicella-zoster, Epstein-Barr, cytomegalo and herpes B viruses, is presented. The article deals with 'in vitro' and 'in vivo' efficacy in animals, animal toxicity, latency and resistance, the mechanism of action and early clinical experience.

The release of beta glucuronidase from the white cells of patients with drug rashes when incubated in autologous plasma, with and without the addition of the causal drug.

In seven out of 16 patients with drug rashes, the leucocytes selectively released beta glucuronidase when incubated in autologous plasma, indicating the possible presence of immune complexes. When the white cells were incubated with the suspected drug in vitro, they tended to react in three different ways. In four out of 16 cases additional beta glucuronidase was released, perhaps due to the formation of immune complexes, in two out of the 16, beta glucuronidase release was suppressed, perhaps due to antigen excess, and in two cases LDH release was decreased while beta glucuronidase remained unaltered.

The release of beta glucuronidase from leukocytes in the presence of immune complexes.

The lysosomal enzyme beta glucuronidase was selectively released from leukocytes when these were incubated with insoluble immnue complexes and also from the leukocytes of patients with immune complex disease when these were incubated with their own plasma.

Acyclovir prophylaxis against herpes virus infections in severely immunocompromised patients: randomised double blind trial.

Twenty patients undergoing allogeneic bone marrow transplantation and 39 patients receiving remission induction chemotherapy for acute leukaemia were entered into a double blind, placebo controlled stratified trial of acyclovir prophylaxis against herpes group virus infections. Within the transplant group intravenous acyclovir 5 mg/kg twice daily given throughout the period of granulocytopenia completely prevented oropharyngeal herpes simplex virus infection compared with a 50% incidence in the placebo arm (p = 0.033). The acyclovir group also had fewer days of fever during the trial and a shorter duration of leukopenia, possibly because of the prevention of herpes simplex virus infections. There was a high incidence of herpes infections after the trial in patients who received either acyclovir or placebo. In the non-transplant group there was also a significant reduction of herpes simplex virus infection in the oropharynx and oesophagus (two out of 19 patients as compared with 10 out of 20; p = 0.018). Herpes simplex virus was isolated in the acyclovir arm within a day after starting the trial in one patient, and the other failure was due to a virus with reduced sensitivity to acyclovir in a patient who had had several previous courses of the drug. The incidence of herpes infections after stopping treatment was low. The influence of acyclovir on excretion of Epstein-Barr virus in saliva in either group was inconclusive. One patient (transplant group) developed a cytomegalovirus infection while receiving acyclovir. Acyclovir provides effective prophylaxis against oropharyngeal and oesophageal herpes simplex virus infection in severely immunocompromised seropositive (greater than or equal to 1/8) patients. In patients given bone marrow transplants this may have the additional benefit of reducing the time to recovery of an adequate blood count and the number of days of fever.