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The route of administration is a major determinant of the onset and duration of a drug's pharmacological effects. Intravenous injection ensures that all of the administered drug is available to the circulation. The rate of drug injection or infusion can be used to control completely the rate of drug availability. However, few psychopharmacological drugs are administered intravenously. Intramuscular administration is commonly thought to produce a rapid onset of effect, but exceptions have been documented. For example, drug absorption by this route was slow and erratic with chlordiazepoxide (Greenblatt et al. 1974). The recent availability of intramuscular forms of some atypical antipsychotics will be advantageous for treating psychotic states when rapid tranquilization is desired and oral administration is impractical. For drugs that are equally well absorbed by the intramuscular and oral routes of administration, the total systemic exposure (as reflected in the area under the plasma concentration–time curve [AUC]) from the two routes should be similar, as should the elimination half-life. A major difference is that the rate of absorption from the intramuscular route may be more rapid. Intramuscular administration of olanzapine 5 mg produced a maximum plasma concentration five times higher than the maximum plasma concentration produced by a 5-mg oral dose with a similar AUC from both routes of administrations (Bergstrom et al. 1999). Most psychoactive drugs are highly lipophilic compounds, which are well absorbed when taken orally. More than 60% of the drugs available on the market are for oral use because of the ease of administration and efficiency of absorption, together with greater patient compliance.

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FIGURE 8–2. Predicted plasma concentration curves following single doses of a drug by rapid intravenous injection (I), a dosage form with complete bioavailability (II), a dosage form with reduced bioavailability (III), and an extended-release dosage form that reduces the rate but not the completeness of absorption (IV).MEC = minimal effective concentration.

FIGURE 8–3. Predicted concentration of a drug in plasma and tissue following a rapid intravenous injection.MEC = minimal effective concentration.

FIGURE 8–4. Effect of protein binding on distribution of drug between plasma and tissue.
Table Reference Number
TABLE 8–1. Substrates, inhibitors, and inducers of the major human liver cytochrome P450 (CYP) enzymes involved in drug metabolism

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