A Review of the Pharmacokinetics of Abacavir

@article{Yuen2008ARO,
  title={A Review of the Pharmacokinetics of Abacavir},
  author={Geoffrey J. Yuen and Stephen Weller and Gary E. Pakes},
  journal={Clinical Pharmacokinetics},
  year={2008},
  volume={47},
  pages={351-371}
}
Abacavir is a carbocyclic 2′-deoxyguanosine nucleoside reverse transcriptase inhibitor that is used as either a 600-mg once-daily or 300-mg twice-daily regimen exclusively in the treatment of HIV infection. Abacavir is rapidly absorbed after oral administration, with peak concentrations occurring 0.63–1 hour after dosing. The absolute bioavailability of abacavir is approximately 83%. Abacavir pharmacokinetics are linear and doseproportional over the range of 300–1200 mg/day. To date, one study… 
PharmGKB summary: abacavir pathway
TLDR
Abacavir is generally well tolerated, and common side effects include nausea, headache, and diarrhea, however, ~ 5–8% of patients experience a hypersensitivity reaction (HSR) within the first 6 weeks of treatment.
The pharmacokinetics of abacavir 600 mg once daily in HIV-1-positive pregnant women
TLDR
The pharmacokinetics of abacavir 600 mg q.d. during pregnancy are equivalent to postpartum and no dose adjustments are required during pregnancy and similar antiviral activity is expected.
Pharmacokinetic study of once-daily versus twice-daily abacavir and lamivudine in HIV type-1-infected children aged 3–<36 months
TLDR
The data suggest that once-daily abacavir and lamivudine might be an option for children aged 3-<36 months, and bioequivalence was demonstrated on AUC(0-24) between twice-daily and once- daily abacvir.
Pharmacokinetics, Safety, and Tolerability of a Single Oral Dose of Abacavir/Dolutegravir/Lamivudine Combination Tablets in Healthy Japanese Study Participants
TLDR
A modest increase in exposure to dolutegravir vs previous clinical studies was observed but is not expected to impact the clinical management of HIV-1 or increase the risk for adverse events.
Population pharmacokinetics of abacavir in infants, toddlers and children.
TLDR
The model demonstrated good predictive performance for dosing prediction in individual patients and can be used to support therapeutic drug monitoring in conjunction with sparse sampling, and appears to be affected only by differences in size, irrespective of the patient's age.
Bioequivalence study of abacavir 300 mg tablets in healthy Thai male volunteers under fasting conditions
TLDR
Two formulations of abacvir, Abacavir GPO and Ziagenavir™, were bioequivalent and can be used interchangeably and both the formulations were well tolerated.
Pharmacokinetics of nucleoside/nucleotide reverse transcriptase inhibitors for the treatment and prevention of HIV infection
TLDR
The pharmacokinetic characteristics of approved NRTIs that are currently in the international treatment and prevention guidelines are summarized and a promising long-acting nucleoside reverse transcriptase translocation inhibitor, islatravir, was well tolerated and remained effective for up to a year, suggesting its potential as a single agent for PrEP.
Abacavir Pharmacogenetics – From Initial Reports to Standard of Care
TLDR
Pharmacogenetic screening to ensure individuals who carry HLA‐B*57:01 do not receive abacavir can reduce the incidence of HSR and is now considered the standard of care before prescribing abacvir.
Abacavir/lamivudine fixed-dose combination antiretroviral therapy for the treatment of HIV
TLDR
ABacavir/lamivudine is reviewed as a treatment for HIV and limitations of its use are discussed, including those at risk for cardiovascular disease and in those with high viral loads before treatment initiation.
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References

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Pharmacokinetics of Abacavir in HIV-1-Infected Patients with Impaired Renal Function
TLDR
In patients with HIV-1-infected patients with various degrees of renal dysfunction, absorption, elimination and distribution phases were not altered by renal insufficiency, and pharmacokinetic data are similar to those obtained in patients with normal renal function.
Safety and Single-Dose Pharmacokinetics of Abacavir (1592U89) in Human Immunodeficiency Virus Type 1-Infected Children
TLDR
It is shown that abacavir is safe and well tolerated in children when it is administered as a single oral dose of 4 or 8 mg/kg.
Multiple-Dose Pharmacokinetics and Pharmacodynamics of Abacavir Alone and in Combination with Zidovudine in Human Immunodeficiency Virus-Infected Adults
TLDR
Abacavir has predictable pharmacokinetic characteristics following the administration of multiple doses following oral administration of daily doses that ranged from 600 to 1,800 mg, with and without zidovudine.
Pharmacokinetic and Pharmacodynamic Study of the Human Immunodeficiency Virus Protease Inhibitor Amprenavir after Multiple Oral Dosing
TLDR
The pharmacodynamic relationship defined in this study supports the use of 1,200 mg b.i.d. as the approved dose of amprenavir, an inhibitor of the protease enzyme of human immunodeficiency virus (HIV) type 1.
Safety and Pharmacokinetics of Abacavir (1592U89) following Oral Administration of Escalating Single Doses in Human Immunodeficiency Virus Type 1-Infected Adults
TLDR
It is shown that abacavir is safe and is well tolerated by HIV-infected subjects and demonstrated predictable pharmacokinetic characteristics when it was administered as single oral doses ranging from 100 to 1,200 mg.
Population Pharmacokinetics and Pharmacodynamic Modeling of Abacavir (1592U89) from a Dose-Ranging, Double-Blind, Randomized Monotherapy Trial with Human Immunodeficiency Virus-Infected Subjects
ABSTRACT Abacavir (formerly 1592U89) is a carbocyclic nucleoside analog with potent anti-human immunodeficiency virus (anti-HIV) activity when administered alone or in combination with other
A Phase I Study of Abacavir (1592U89) Alone and in Combination With Other Antiretroviral Agents in Infants and Children With Human Immunodeficiency Virus Infection
TLDR
Abacavir therapy is associated with good short-term tolerance and safety in HIV-infected children and Phase III studies are in progress to assess the antiviral activity of abacvir in children and adults.
Single-Dose Pharmacokinetics and Safety of Abacavir (1592U89), Zidovudine, and Lamivudine Administered Alone and in Combination in Adults with Human Immunodeficiency Virus Infection
TLDR
No clinically significant pharmacokinetic interactions occurred between abacavir, ZDV, and 3TC in HIV-1-infected adults and these agents were generally well tolerated and did not produce unexpected adverse events.
Methadone Blood Concentrations Are Decreased by the Administration of Abacavir Plus Amprenavir
TLDR
Methadone blood concentrations were measured in five addict patients receiving methadone maintenance therapy before and after introduction of abacavir plus amprenavir, showing a significant reduction in concentration.
Pharmacodynamics of Abacavir in an In Vitro Hollow-Fiber Model System
TLDR
The hollow-fiber pharmacodynamic modeling system concludes that the dose of abacavir currently being studied in clinical trials (300 mg orally q12h) will be efficacious for the majority of sensitive clinical isolates of HIV-1 and suggests that this drug may be able to be administered to patients on a once-daily basis at a dose of 600 mg.
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