Pharmacokinetics: absorption

• Proportionally more of basic drugs are absorbed in older patients than younger patients
• Acidic drugs require an acidic environment for absorption (pH < 7.35), whereas basic drugs require a basic environment for absorption (> 7.35)
• As we age, there is increased gastric pH (decreased acid) and small bowel surface area decreases
• Usually not a problem except if:
  • Previous GI surgery
  • NJ tube or PEG feed composition
  • Transdermal patches and oedema
• Think about best route of delivery to aid absorption
  • Liquid/syrup for dysphagia
  • Can tablets be crushed for PEG or NG tube
  • Confused patients refusing tablets/acute agitation
  • NBM pts for surgery or investigations

Pharmacokinetics: distribution

Protein binding

• Free vs. bound proportion of drugs
• There are two main binding proteins:
  • Albumin (basic) binds to acidic drugs
  • Alpha-1 acid glycoprotein (acidic) binds to basic drugs
• Elderly often have lo albumin bind higher A-1 AG

Lipid binding

• Older patients have increased fat (proportional to muscle mass)
• This increases the Vd of lipophylic drugs e.g. diazepam, anaesthetics, which results in a longer half life
  • Volume of distribution (Vd): theoretical volume into which all of drug is fully dissolved in plasma
    • It is an indicator of lipophilicity of drugs (very lipophilic = high Vd)
  • Half-life: time for drug concentration to fall to half of its maximum concentration

Body water

• Body water decreases by 10-15% with age
• This lowers the Vd of hydrophobic drugs
• Lower Vd AND lower CrCL means t1/2 is usually unchanged significantly in the elderly but this is not always the case

Pharmacokinetics: metabolism and excretion

Hepatic metabolism