Biomedical subjects

David W Kimberlin

Publications and source records attributed to David W Kimberlin.

21 records · Page 2Linked to original sources

PubMed2002

Antiviral therapy for cytomegalovirus infections in pediatric patients.

Appreciation of the spectrum of illness caused by cytomegalovirus (CMV) infections has increased markedly during the past 2 decades. The number of immunosuppressed patients also has increased during the same time period, reflecting the central tenet that CMV disease is most severe in this patient population. Fortunately, antiviral therapies with activity against CMV also have been identified during this same time course, and they include ganciclovir, foscamet, and cidofovir. Although all 3 of these therapies can have significant toxicities associated with them, nonetheless they are employed with relative frequency to treat potentially life-threatening CMV disease. Ganciclovir is the first-line compound used, followed by foscarnet and cidofovir. This article summarizes those CMV infections that require antiviral therapy and outlines therapeutic options for each.

AIDS-Related Opportunistic Infections↗

PubMed2002

Pharmacotherapy of recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis (RRP) is a disease which affects both children (juvenile-onset RRP) and adults (adult-onset RRP). While a greater amount of information is known about the epidemiology of juvenile-onset than adult-onset RRP, fundamental work is still needed to more fully describe areas such as the mode of transmission. The primary management approach focuses on the removal of the papillomas by surgical debulking, although persistence of the human papillomavirus genome and subsequent recurrence of disease is the typical outcome. In a minority of patients, surgical management must be supplemented with adjuvant medical therapy, with IFN being the best studied and most commonly used. Other adjuvant treatments being employed include photodynamic therapy, indole-3-carbinol, ribavirin and cidofovir. Large controlled trials are lacking for all but IFN, making it extremely difficult to assess clinical benefit and risk in a systematic fashion at the current time. As with surgical management, viral persistence occurs following treatment with these adjuvant modalities, further contributing to the challenge of managing patients with this potentially devastating disease.

Adolescent↗

PubMed2002

Antiretroviral pharmacokinetics in the paediatric population: a review.

Characteristics unique to paediatric pharmacotherapy should be considered when treating children infected with human immunodeficiency virus (HIV). Processes of growth and development in the paediatric patient can significantly affect drug absorption and disposition. Immature renal function, altered hepatic enzyme activity and differences in drug absorption lead to variations in systemic exposure of antiretrovirals among children. Paediatric patients are also subject to unique circumstances that may prevent adherence to antiretroviral regimens. The pharmacokinetics of nucleoside reverse transcriptase inhibitors differ significantly among preterm infants, full-term infants and older children. Decreased hepatic glucuronidation activity in neonates results in pharmacokinetic differences in zidovudine disposition when compared with older children. Didanosine, stavudine and lamivudine are renally eliminated, thus resulting in differences among young children with immature renal function. Pharmacokinetic data for non-nucleoside reverse transcriptase inhibitors in children are limited. Decreased elimination of nevirapine among neonates has been observed, primarily due to decreased enzymatic activity. Pharmacokinetic differences across age groups have been noted for efavirenz, but no formal assessments have been conducted in children weighing less than 10kg. Protease inhibitors are metabolised by the cytochrome P450 enzyme system, which is not fully developed in younger children. Decreased metabolism can result in elevated plasma concentrations, thereby increasing the chance of toxicity. Unfortunately, few studies exist evaluating the pharmacokinetics of antiretrovirals in children. As a result, dosage selection of antiretrovirals in children often occurs without adequate data. As the life expectancy of HIV-infected children increases, use of antiretrovirals to prevent disease progression also increases. If prevention of treatment failure continues to be the goal of antiretroviral therapy, the pharmacokinetics of antiretrovirals in children need to be assessed early in the drug development process.

Age Factors↗