VIH e o Envelhecimento

Drug-drug Interactions and Polypharmacy in Older HIV Persons

Polymedication and drug metabolism in aging patients

Pharmacokinetic changes in the elderly

The increase in gastric pH and changes in the structure of the small intestine (decreased small bowel surface area) can lead to reduced drug absorption and increased inter-individual variability. However, increasing age is most often associated with increa- sed concentrations of antiretroviral drugs. Several mechanisms may explain this phenomenon:

  • Regarding metabolism, some CYP450 forms may act less ef- ficiently with age, such as CYP4502c19 which is responsible for the metabolism of omeprazole. So, it may occur increa- sed drug concentration with toxicity and drug interactions. In addition, the reductions in liver volume and blood flow can decrease the hepatic clearance of drugs;
  • The distribution of drugs is also affected by age, particularly with the increase of adipose tissue and reduction of muscle tissue, which can lead to drug accumulation and toxicity;
  • The distribution of the drugs may be modified in very elderly subjects by an alteration of the integrity of the barriers (as in the case of the blood-brain barrier). However, it is unknown whether these changes may be associated with a loss of efficacy or increased toxicity;
  • Renal clearance may be impaired with age, with decreased glomerular filtration rate. For example, a pharmacokinetic study with TDF verified significantly higher concentrations in people over 60 years of age.9
  • Winston et al. found that concentrations of PI seem to increase with age while other drugs such as efavirenz (EFV), do not seem to be affected;10
  • In a phase 1 pharmacokinetic study, Vera et al. found that there were no differences in the RAL concentrations between individuals over 60 years old and younger individuals, which may be explained by the fact that RAL is eliminated by glucuronidation and phase 2 enzymes are not as affected by age;11
  • A prospective observational study that is being conducted in the UK and the Netherlands (Poppy study) will soon provide more information about the impact of age on the pharmacokinetics in elderly;12

Autor: Marta Boffito, MD PhD (Chelsea and Westminster Hospital, London, UK)

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