Antipsychotics 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. 

Available kinetic data for the conunonly prescribed typical antipsychotics are presented in Table 9.1. The noted references are reconunended for reviews of antipsychotic pharmacokinetics and therapeutic response. - ... 

Risperidone (11) was also included among a a 1-adrenergic receptor antagonists to study a quantitative structure-activity relationship (99BMC2437). A pharmacophore model for atypical antipsychotics, including 11, was established (00MI41). An increased plasma level of 11 and 9-hydroxyrisperidone (12) was observed in combination with paroxetine (01 MI 13). The effect of vanlafaxine on the pharmacokinetics of 11 was reported (99MI13). 

Medications that have been used as treatment for anxiety and depression in the postwithdrawal state include antidepressants, benzodia2epines and other anxiolytics, antipsychotics, and lithium. In general, the indications for use of these medications in alcoholic patients are similar to those for use in nonalcoholic patients with psychiatric illness. However, following careful differential diagnosis, the choice of medications should take into account the increased potential for adverse effects when the medications are prescribed to alcoholic patients. For example, adverse effects can result from pharmacodynamic interactions with medical disorders commonly present in alcoholic patients, as well as from pharmacokinetic interactions with medications prescribed to treat these disorders (Sullivan and O Connor 2004). 

Chiu et al, 1992 Lin Finder, 1983 Lin et al, 1988b Potkin et al, 1984 Lin etal., 1989 Ruiz et al, 1996 Jann et al, 1989 Jann etal, 1992 Zhang-Wong etal., 1998). The majority of these studies were carried out with haloperidol. A number of studies examined differences between Caucasians and Hispanics, and African Americans and Caucasians (Midha et al., 1988b Midha etal, 1988a Ruiz et al., 1996). In general these studies provided mixed results. Another noteworthy feature of the research literature is that there appear to be no studies that have considered ethnic differences in pharmacokinetics and response for the depot antipsychotics. This may be an artifact of the low levels of depot prescribing found in the US, China, and Japan. 

Caccia, S. (2000). Biotransformation of post-clozapine antipsychotics pharmacological implications. Clin. Pharmacokinet., 38, 393-414. 

Kubo, M. et al. (2005). Influence of itraconazole co-administration and CYP2D6 genotype on the pharmacokinetics of the new antipsychotic Aripriprazole. Drug Metab. Pharmacokinet.,... 

It is widely held that differences exist in the usage and dosage of antipsychotics among ethnic minority groups. A number of factors are felt to account for these differences and include sociocultural variables (racial bias, cultural divide between patient and physician, language), as well as biological variables (pharmacogenetic, pharmacokinetic, and pharmacodynamic). 

Compared to antipsychotics, there are even fewer studies on the prescribing patterns of antidepressants done in Asian countries. Pi etal. (1985) conducted a survey of psychotropic prescribing practices reported by psychiatrists in 29 medical schools in 9 Asian countries. Daily dose range of tricyclic antidepressants (TCAs) such as amitriptyline, imipramine, and nortriptyline in Asian countries was comparable to the practice in USA. This is despite differences found between Asian and non-Asian populations in the pharmacokinetics of TCAs (Pi et al, 1993). A questionnaire on the practical prescribing approaches in mood disorders administered to 298 Japanese psychiatrists was reported by Oshima et al. (1999). As first-line treatment, the majority of respondents chose newer TCAs or non-TCAs for moderate depression and older TCAs for severe depression. Combination of antidepressants and anxiolytics was preferred in moderate depression, while an antidepressant and antipsychotic combination was common in severe psychotic depression. Surprisingly, sulpiride was the most favored drug for dysthymia. In a naturalistic, prospective follow-up of 95 patients with major depression in Japan, the proportion of patients receiving 125 mg/day or less of imipramine was 69% at one month and 67% at six months (Furukawa et al., 2000). 

Jeste DV, Lacro JP, Palmer B et al. (1999) Incidence of tardive dyskinesia in early stages of low-dose treatment with typical antipsychotics in older patients. Am I Psychiatry 156(2) 309-311 Klotz U (1998) Effect of age on pharmacokinetics and pharmacodynamics in man. Int I Clin Pharmacol Ther 36(11) 581-585... 

A recent study determined the myocardium to plasma concentration ratios of five antipsychotics and underscored the importance of interpreting hERG channel and electrophysiological data in conjunction with other pharmacokinetic parameters [114]. 

Mechanism of Action An antipsychotic agent that provides partial agonist activity at dopamine and serotonin (S-HTj ) receptors and antagonist activity at serotonin (5-HTja) receptors. Therapeutic Effect Diminishes schizophrenic behavior. Pharmacokinetics Well absorbed through the GI tract. Protein binding 99% (primarily albumin). Reaches steady levels in 2 wk. Metabolized in the liver. Eliminated primarily in feces and, to a lesser extent, in urine. Not removed by hemodialysis. Half-life 75 hr. 

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