Final answer:
Drugs with a high first-pass effect require a higher oral-to-parenteral dose ratio when given orally to compensate for the significant reduction of the drug's active substance due to liver metabolism and to achieve therapeutic plasma levels.
Step-by-step explanation:
Drugs with a high first-pass effect must have a higher oral-to-parenteral dose ratio if they are given orally. This is because the first-pass effect refers to the metabolism of a drug within the liver after oral administration, which can significantly reduce the amount of active drug reaching systemic circulation. To achieve therapeutic plasma levels similar to those achieved via parenteral routes like intravenous or intramuscular injections, a greater dose is often required when the drug is administered orally.