Pharmacokinetic modeling to determine the minimum effective dose of disease-specific antibodies for preventing hepatitis A post-exposure

ABSTRACT

Background

The minimum effective dose of intramuscular polyvalent immune globulin for prevention of hepatitis A post-exposure is unknown. In Australia current dosing is according to weight category.

Methods

The peak concentration and decay of hepatitis A antibodies after intramuscular dosing of immune globulin in adults was modeled utilizing published parameters. Models simulated dosing according to current Australian guidelines, then adjusted the dose in clinically relevant increments to estimate the optimal dose of hepatitis A antibodies for post-exposure prophylaxis of nonimmune individuals. Optimal dosing assumed a target serum concentration of hepatitis A antibodies of the correlate of protection plus a 10% margin of error at an incubation period. The effect of weight on hepatitis A antibody concentration at an incubation period under current guidelines was examined by fixing weight in 5 kg increments.

Results

Current dosing guidelines in Australia may underdose people who weigh in excess of 85 kg. The optimal dose of hepatitis A-specific antibodies according to the model was 3.6, 2.5, and 1.9 IU/kg assuming 50%, 75% and 100% bioavailability respectively.

Conclusions

For individuals in Australia recommended passive immunization as post-exposure prophylaxis and weighing in excess of 85 kg, conservative management would include dosing between 2.5 and 3.6 IU hepatitis A antibodies/kg.

KEYWORDS:

• Immunoglobulin
• passive immunization
• hepatitis A
• pharmacokinetics
• post-exposure prophylaxis

Article highlights

• Current Australian guidelines recommend passive immunization for post-exposure prophylaxis of hepatitis A to a group at high risk of complications and dose according to weight category.

• As the upper weight category is >50 kg, dosing by weight category may underdose those above a certain weight.

• This pharmacokinetic modeling study suggests current Australian dosing may underdose people weighing more than 85 kg.

• The optimal dose of hepatitis A antibodies for post-exposure prophylaxis in a nonimmune adult population appears to be between 2.5 and 3.6 IU/kg assuming 75% and 50% bioavailability respectively.

• The model may be adapted for use internationally.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

MY was responsible for conception of the study, assisted with the design and data collection, interpreted the results and drafted the paper.

SKN assisted with the design and data collection, was responsible for data analysis, and critically revised the paper for intellectual content.

GN assisted with interpretation of the results and critically revised the paper for intellectual content.

AC assisted with design of the study, and interpretation of results and critically revised the paper for intellectual content.

All authors agree to be accountable for all aspects of the work.

Additional information

Funding

This paper was not funded.