Antipsychotic drugs pharmacokinetics

Antipsychotic pharmacokinetics can be significantly affected by concomitantly administered enzyme inducers or inhibitors. Smoking is a potent inducer of hepatic enzymes and may increase antipsychotic clearance by as much as 50%. The published literature may be consulted for a listing of antipsychotic drug interactions. 

Many of the general principles of pharmacokinetics were introduced in Chapter 6 on antidepressants (see also Figs. 6—8 through 6—20). Here we will discuss some specific pharmacokinetic issues relating to antipsychotic drugs. 

Baptista T, Kin NM, Beaulieu S. Treatment of the metabolic disturbances caused by antipsychotic drugs. Clin Pharmacokinet 2004 43 1-15. 

Milton GV, Jann MW (1995) Emergency treatment of psychotic symptoms. Pharmacokinetic considerations for antipsychotic drugs. Clin Pharmacokinet 28(6) 494-504... 

Drug interactions with lithium have been reviewed (569-573) another review focused on interactions in the elderly (573). A review of drug interactions with lithium considered both pharmacokinetic interactions [for example diuretics, nonsteroidal anti-inflammatory drugs (NSAIDs)] and pharmacodynamic interactions (for example antipsychotic drugs, SSRIs) and summarized the most important ones in tabular form (569). 

The steady-state concentrations of antipsychotic drugs after multiple dosing have been measured to establish a relationship between plasma concentrations and clinical efficacy or to monitor adverse effects (360-363). The majority of drugs in the class seem to exhibit linear pharmacokinetics, despite the wide interindividual variations in pharmacokinetic properties observed for specific agents. Linear pharmacokinetics allows the dosage to be readily adjusted if the steady-state plasma concentration is in the sub-therapeutic or toxic range. 

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. 

Dahl, S. G., Plasma level monitoring of antipsychotic drugs clinical utility, Clin. Pharmacokinet, 11 36-61, 1986. 

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