Antipsychotic drugs intramuscular administration

The clinical pharmacodynamics and pharmacokinetics of molindone (91) have been reviewed (525). The drug is reputed to be rapidly absorbed after oral administration and rapidly metabolized. Only 2-3% of the unchanged drug can be recovered in the urine and feces. Molindone has a very short half-like (1.5-2 h) and is 1.5-1.7 times more bioavailable after intramuscular, rather than oral, administration (526). Molindone is less lipophilic than most antipsychotic drugs and has a lower fraction (around 75%)that is bound to proteins in the plasma (527).Clinical studies indicate that the antipsychotic effectiveness of molindone lasts more than 24 h (525,528,5291, suggesting that one or more active metabolites may contribute to its actions in vivo. 

ABSORPTION, DISTRIBUTION, FATE, AND EXCRETION Some antipsychotic drugs have erratic and unpredictable patterns of absorption after oral administration. Parenteral (intramuscular) administration increases the bioavaftabUity of active drug 4-10-fold. Most antipsychotic drugs are highly lipophilic, highly membrane- or protein-bound, and accumulate in the brain, lung, and other tissues with a rich blood supply. They also enter the fetal circulation and breast milk. It is virtually impossible to remove these agents by dialysis. 

With several antipsychotic agents, bioavailability and drug acceptance by hospitalized patients is somewhat increased with liquid concentrates and rapidly disintegrating tablets that yield peak serum concentrations of chlorpromazine and other phenothiazines within 2— hours. Intramuscular administration avoids much of the first-pass enteric metabolism and provides measurable concentrations in plasma within 15-30 minutes. Bioavailability of chlorpromazine may be increased up to tenfold with injections, but the clinical dose usually is decreased by only three- to fourfold. 

Conversely, certain forms of intramuscular antipsychotics that enter the bloodstream slowly have been developed. This method of depot administration may prove helpful if the patient has poor selfadherence to drug therapy and neglects to take his or... 

---