Clinicians can use therapeutic drug monitoring(TDM) to optimise dosage decisions with psychotropic drugs, in order to maximize efficacy and prevent toxicity, especially when individuals are nonresponsive to treatment or vulnerable to adverse reactions with standard doses because age, disease states or drug interactions. Currently therapeutic drug concentrations have been established for the TCA and lithium. There is also evidence for the usefulness of TDM with carbamazepine, valproic acid and some antipsychotic drugs. However for most psychotropic drugs this approach remains experimental. TDM-assisted psychiatric treatment is potentially useful and cost effective, particularly when applied by psychiatrists who are knowledgeable of pharmacokinetics and pharmacodynamics.
Antipsychotic Agents ; Carbamazepine ; Drug Interactions ; Lithium ; Pharmacokinetics ; Psychiatry ; Psychotropic Drugs* ; Valproic Acid

To investigate the effects of carbamazepine (CBZ) on the plasma concentrations of valproic acid (VPA) and its toxic metabolite 2-propyl-4-pentenoic acid (4-ene VPA) in epileptic patients, the plasma concentrations of VPA and 4-ene VPA were determined, and the effect of CBZ on pharmacokinetics of VPA was evaluated. All patients had been divided into two groups (VPA group, n = 87; and VPA+CBZ group, n = 19). As compared to VPA group, the combination of CBZ significantly (P < 0.01) decreased the trough concentration of VPA [VPA group, (69.5 +/- 28.8) microg x mL(-1); VPA+CBZ group, (46.3 +/- 25.6) microg x mL(-1)] and does-adjusted VPA trough concentration [VPA group, (4.89 +/- 2.21) microg x mL(-1) x mg(-1) x kg(-1); VPA+CBZ group, (3.14 +/- 1.74) microg x mL(-1) x mg(-1) x kg(-1)]. However, the addition of CBZ did not influence the concentration of 4-ene VPA. The present study revealed that coadministration of CBZ can reduce VPA plasma concentration and may impact VPA clinical effect, therefore therapeutic drug mornitoring of VPA should be used when combined use of CBZ and VPA.
Adolescent ; Adult ; Anticonvulsants ; blood ; pharmacokinetics ; therapeutic use ; Carbamazepine ; blood ; pharmacokinetics ; therapeutic use ; Drug Interactions ; Drug Therapy, Combination ; Epilepsy ; blood ; drug therapy ; Fatty Acids, Monounsaturated ; blood ; Female ; Humans ; Male ; Valproic Acid ; blood ; pharmacokinetics ; therapeutic use ; Young Adult

Recently attention to the behavior and psychological symptoms of dementia (BPSD) is increasing repidly. Agitation is one of the BPSDs that contributes to the heavy burden on the caregiver and family. But, the definition of the agitation is controversial, and the rating scales for its measurements have limitations. We reviewed the literatures and our experiences to propose a rational strategy for controlling the agitating behaviors in the demented elderly. In the assessment of agitation in dementia, the top priority is a careful evaluation of the patient's medical, psychiatric, and environmental status. After pertinent medical conditions have been identified and managed, significant agitation may still be present and require intervention. Basically both behavior/environmental intervention and psychopharmacologic management are recommended in almost all situations. For patients with mild agitation, the clinician may consider implementing behavioral/environmental intervention singwarly. In severe agitation, however, pharmacologic approach is a preferred strategy, and can be administered according to the prevailing syndromes, such as psychosis, depression, delirium, anxiety, and so on. In practice high potency conventional antipsychotics and benzodiazepines are fregnently prescribed, but recently, drugs that have fewer long-term side effects, such as risperidone and divalproex are highly recommended. Due to the decreased pharmacokinetics and pharmacodynamics, drug dosages for the demented elderlies are much lower compared to younger patients. Side effects of the maintaining psychotropics should be monitored cautiously as well. Although some patients require long-term treatment, it is important to taper off and discontinue the medication periodically following a satisfactory improvement.
Aged ; Antipsychotic Agents ; Anxiety* ; Benzodiazepines ; Caregivers ; Delirium ; Dementia ; Depression ; Dihydroergotamine* ; Drug Therapy ; Humans ; Pharmacokinetics ; Psychotic Disorders ; Risperidone ; Valproic Acid ; Weights and Measures

We investigated the single- and multiple dose pharmacokinetics of a new controlled-release formulation (Orfil retard enteric coated tablet) of valproic acid in comparison with those of the plain tablet as a reference. Twelve healthy volunteers were given each formulation of 300 mg in the single-dose study. In the steady-state multiple-dose study, twelve epileptic patients received 1200 mg/day of the reference drug (300 mg 9 AM, 300 mg 3 PM, 600 mg 9 PM) and the test formulation (600 mg 9 AM, 600 mg 9 PM) with at least one week interval in cross-over manner. The AUC values of the test controlled release formulation were 91.7% (95% confidence interval: 78.4-100.4%) of the reference drug in the single-dose study and 98.2% (95% confidence interval: 86.2%-109.9%) in the steady-state study. The AUC's of the two formulations were not significantly different by ANOVA test. The Cmax and Tmax values of the test formulation were significantly different from the values of the reference in single-(Tmax: 158.4%, Cmax: 52.5% of the reference) and multiple-dose study (Tmax: 153.5% of the reference). The MRT values of the test formulation were also significantly greater (129.4% of the reference) in the single-dose study. Regarding the controlled-release characteristics of the test formulation, fluctuation index and percentage fluctuation of the twice a day dosage regimen of the test formulation were comparable with those of the thrice a day dosage regimen of the conventional tablet. Area deviation was even smaller in the test regimen of the controlled release formulation.(ABSTRACT TRUNCATED AT 250 WORDS)
Administration, Oral ; Adult ; Biological Availability ; Delayed-Action Preparations ; Epilepsy/blood/*drug therapy ; Humans ; Male ; Tablets ; Tablets, Enteric-Coated ; Valproic Acid/*pharmacokinetics

Burkitt lymphoma is a highly aggressive B-cell neoplasm. New therapeutic methods are needed to overcome the adverse effect of intensive chemotherapy regimens. Valproic acid and (-)-gossypol are two kinds of chemical compounds used as new anti-tumor drugs in recent years. To investigate the anti-tumor effect of valproic acid and (-)-gossypol, Burkitt lymphoma Namalwa cells were cultured and treated with valproic acid and (-)-gossypol at different concentrations. The proliferation of Namalwa cells was dramatically suppressed after the combination treatment with 2 mmol/L valproic acid and 5 μmol/L (-)-gossypol. The combined treatment also enhanced intrinsic apoptosis by down-regulating anti-apoptotic protein Mcl-1. Moreover, the autophagy flux significantly increased in Namalwa cells after combined treatment. However, the enhanced autophagy showed little effect on cell survival with present regimen. The results confirmed that combination of valproic acid and (-)-gossypol had synergistic anti-tumor effect to Burkitt lymphoma Namalwa cells. The related mechanisms might include the down-regulation of anti-apoptotic protein Mcl-1 and avianized pro-survival role of autophagy.
Antineoplastic Agents ; administration & dosage ; pharmacokinetics ; therapeutic use ; Apoptosis ; drug effects ; Burkitt Lymphoma ; drug therapy ; Cell Line, Tumor ; Contraceptive Agents, Male ; administration & dosage ; pharmacokinetics ; therapeutic use ; Drug Synergism ; Enzyme Inhibitors ; administration & dosage ; pharmacokinetics ; therapeutic use ; Gene Expression Regulation, Neoplastic ; drug effects ; Gossypol ; administration & dosage ; pharmacokinetics ; therapeutic use ; Humans ; Valproic Acid ; administration & dosage ; pharmacokinetics ; therapeutic use