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PubMed1996

Concentration-related pharmacodynamic effects of thioridazine and its metabolites in humans.

OBJECTIVE: To measure cardiac and other effects of thioridazine and relate these to the plasma concentration of the parent drug and its principal metabolites. METHODS: A double-blind, randomized-order crossover study involving nine healthy male subjects compared the effects of single doses of thioridazine (10 mg and 50 mg) with placebo. Plasma concentrations of thioridazine and its ring sulfoxide, side-chain sulfoxide, and side-chain sulfone metabolites were measured, together with effects on the ECG, blood pressure, salivary flow, and a batch of psychomotor tests for 72 hours after administration. RESULTS: Thioridazine, 50 mg, reduced standing systolic blood pressure (mean peak changes from baseline [95% CI] -32 mm Hg [-55, 10 mm Hg]; p < 0.01 versus placebo) and diastolic blood pressure (-14 mm Hg [-26, -2 mm Hg]; p < 0.05), increased standing heart rate (7 beats/min [-1, 16 beats/min]; p < 0.05), impaired psychomotor function, and prolonged the JT (20 ms1/2 [7, 34 ms1/2]; p < 0.05), QTa (22 ms1/2 [8, 36 ms1/2]; p < 0.05), and QTc (22 ms1/2 [11, 33 ms1/2]; p < 0.01) intervals, but had no effect on QT dispersion (-12 ms1/2 [-31, 6 ms1/2]). Thioridazine, 1.0 mg, also significantly increased QTc, but the effect was less marked (9 ms1/2 [-1, 19 ms1/2]; p < 0.05). Plasma thioridazine and metabolite concentrations did not correlate significantly with these effects. Maximum effects on QTc occurred after peak concentrations of thioridazine but before peak concentrations of the ring sulfoxide and side-chain sulfone metabolites. CONCLUSIONS: These data suggest that thioridazine has dose-related effects on ventricular repolarization and that the parent drug causes an important proportion of these effects, although its metabolites may also contribute.

Adult↗
PubMed1997

Effects of thioridazine, an inhibitor of CYP2D6, on the steady-state plasma concentrations of the enantiomers of mianserin and its active metabolite, desmethylmianserin, in depressed Japanese patients.

The antidepressant mianserin is administered as a racemate of the S(+)- and R(-)-enantiomers. Previous in-vitro studies have suggested that CYP2D6 is involved in the stereoselective metabolism of mianserin and its active metabolite, desmethylmianserin. To determine a role for CYP2D6 in vivo, the effects of thioridazine, an inhibitor of CYP2D6, on the steady-state plasma concentrations of the enantiomers of mianserin and desmethylmianserin were examined in 13 depressed Japanese patients. All patients were taking 30 mg of racemic mianserin at bedtime for 8-50 days. Thioridazine (40 mg/day) was coadministered for 1 week, and blood samplings were performed before and after thioridazine coadministration, 12 h after bedtime dosing. Plasma concentrations of the enantiomers of mianserin and desmethylmianserin were measured by HPLC, and the CYP2D6 genotype was determined by allele-specific PCR analysis. Thioridazine significantly increased plasma concentration of S(+)-mianserin (mean SD: 78.2 +/- 35.0 vs. 150.8 +/- 48.7 nM, P < 0.001), but not R(-)-mianserin (39.8 +/- 21.2 vs. 39.5 +/- 20.6 nM, NS). Thioridazine also significantly increased plasma concentrations of both S-desmethylmianserin (11.9 +/- 2.8 vs. 24.4 +/- 10.7 nM, P < 0.01) and R-desmethylmianserin (42.6 +/- 28.4 vs. 115.6 +/- 36.9 nM, P < 0.001). One patient homozygous for the defective allele CYP2D6*5 had the second highest and highest plasma concentrations of S(+)-mianserin and R-desmethylmianserin, respectively, before thioridazine coadministration, and exhibited little increase in plasma concentration of the drugs after thioridazine coadministration. These results suggest that thioridazine specifically inhibits the metabolism of S(+)-mianserin and R-desmethylmianserin, probably through inhibition of CYP2D6, but not R(-)-mianserin.

Antidepressive Agents, Second-Generation↗
PubMed1995

Metabolism of thioridazine by microsomal monooxygenases: relative roles of P450 and flavin-containing monooxygenase.

1. The metabolism of thioridazine by the flavin-containing monooxygenase (FMO) of mouse liver and several P450 isozymes was examined using microsomes, purified FMO, and expressed P450 isozymes. Metabolites were identified by hplc. 2. Thermal inactivation and antibodies to NADPH P450 reductase were used to selectively inactivate FMO and P450 respectively. Inactivation of FMO by heat-treatment reduced the formation of thioridazine-N-oxide and northioridazine, whereas inactivation of P450 resulted in decreased amounts of thioridazine-2-sulphoxide, northioridazine, and thioridazine-5-sulphoxide. 3. Liver microsomes from mouse induced with phenobarbital, 3-methylcholanthrene, or acetone were compared with control microsomes. Phenobarbital induction resulted in increased formation of all metabolites except thioridazine-N-oxide, while retaining a general metabolic profile similar to that achieved with control microsomes. Neither 3-methylcholanthrene nor acetone induction had any effect on the in vitro metabolism of thioridazine. 4. FMO purified from mouse liver produced thioridazine-N-oxide as the major metabolite. 5. Preliminary experiments with commercially prepared microsomes made from cells expressing recombinant human liver P450 2D6 and 3A4 suggested that thioridazine is metabolized by 2D6 but not 3A4.

Animals↗
PubMed1980

The comparison of the effects of DL-308, a potential new neuroleptic agent, and thioridazine on some psychological and physiological functions in healthy volunteers.

Eight healthy male volunteers participated in four experimental sessions in which they ingested either DL-308 (10 mg), DL-308 (20 mg), thioridazine (50 mg) or placebo. Drugs were allocated to subjects and sessions in a double-blind fashion according to a balanced cross-over design. Both DL-308 and thioridazine displayed sedative properties, as indicated by the sedated appearance of the subjects, by a decrease in subjectively rated alertness and by an impairment of performance on psychomotor tests. DL-308 appeared to be a more potent sedative than thioridazine. DL-308 (10 mg) caused an increase in subjectivey rated sweating and objectively measured heart rate, suggesting a sympathomimetic property for the drug. DL-308, similarly to thioridazine, had effects consistent with an alpha-adrenolytic action; both drugs caused miosis, hypotension and a decrease in salivation. The decrease in salivation may also be consistent with an anticholinergic effect. When equisedative doses of the two drugs were compared, DL-308 had a much smaller influence on autonomic functions than thioridazine. DL-308 had a faster time-course of action than thioridazine. Peak effects were attained 1-3 h post-drug and the effects almost completely dissipated within 5 h. DL-308, similarly to thioridazine, had little effect on the motor system, as indicated by conventional clinical neurological examination.

Adult↗
PubMed1991

Paradoxical effects of thioridazine on electromechanical coupling in the human and rat vas deferens.

The effects of thioridazine on the responses of isolated human and rat vas deferens to high [K+]0, A23187 and caffeine were examined. In the presence of Ca2+ (2.5 mM), thioridazine (1-10 microM) induced spontaneous contractions but caused a dose-related inhibition of the phasic and secondary parts of the response to high [K+]0 (136 mM). The relaxation phase of the high [K+]0 response of the human vas deferens was unaffected by thioridazine (up to 10 microM). In Ca2(+)-free/EGTA (0.5 mM) media, thioridazine caused a dose-related potentiation, shortened the latency and prolonged the duration of high [K+]0 responses. Contractions to caffeine (20 mM) and A23187 (20-50 microM) were relatively unchanged by thioridazine (10 microM). The spontaneous activity caused by thioridazine (10 microM) was sensitive to the Ca2(+)-channel blockers nifedipine (10 microM) or verapamil (10 microM). These results indicate that the action of thioridazine during electromechanical coupling in the human and rat vas deferens may involve more than its blockade of voltage gated Ca2+ channels.

Animals↗
PubMed1993

Thioridazine induces lipid peroxidation in myelin of rat brain.

In this study, the oxidative effect of the commonly used phenothiazine, thioridazine, on brain tissue has been investigated. Thioridazine (0.1 and 0.5%) supplemented in pellet diet (w/w), produced a significant increase (P < 0.001) in levels of myelin lipid peroxide, after 3 weeks of treatment. Besides myelin, there was a 2-fold increase in the mitochondrial lipid peroxides, as a result of treatment with thioridazine. However, these elevated levels of lipid peroxides returned to normal after withdrawal of thioridazine for 2 weeks. Myelin-associated enzyme activities of Na+,K(+)-ATPase and 5'-nucleotidase became inhibited by 20-25%, but CNPase activity was unaffected. Studies of in vitro lipid peroxidation on purified myelin from untreated rats suggested that extensive lipid peroxidation of myelin in thioridazine-treated rats could underlie inhibition of the myelin enzymes. Morphological studies revealed little or no structural alterations in myelin, produced by thioridazine. These studies suggest that thioridazine induces a reversible lipid peroxidation in myelin, that could result in functional alterations of the myelin-associated enzymes, during use of this drug.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMedDate not supplied

Effects of thioridazine and visual screening on stereotypy and social behavior in individuals with mental retardation.

Thioridazine and visual screening procedures are effective in reducing the stereotypic behaviors of individuals with mental retardation. A double-blind, placebo-controlled study, using alternating treatments within a multiple-baseline across subjects design, was conducted to assess the effects of two doses of thioridazine (1.25 and 2.5 mg/kg/day) and visual screening, alone and combined, on stereotypy and social behavior of three individuals with profound mental retardation. Functional analyses did not show demand, alone, social attention, or differential reinforcement conditions to maintain the subjects' stereotypy. Thioridazine was effective in producing modest reductions in stereotypy and minor increases in social behavior across subjects. The higher dose of thioridazine (2.5 mg/kg/day) was slightly more effective than the lower dose (1.25 mg/kg/day), and thioridazine plus visual screening was more effective than thioridazine alone. The most effective treatment was visual screening when used in the absence of thioridazine. This study demonstrates a method for assessing the impact of psychopharmacological and behavioral interventions in individuals for whom a behavioral treatment cannot be easily derived from a functional analysis of the maintaining conditions of the target behavior.

Adolescent↗
PubMed1991

Plasma levels of thioridazine and metabolites are influenced by the debrisoquin hydroxylation phenotype.

The pharmacokinetics of thioridazine and its metabolites were studied in 19 healthy male subjects: 6 slow and 13 rapid hydroxylators of debrisoquin. The subjects received a single 25 mg oral dose of thioridazine, and blood samples were collected during 48 hours. Concentrations of thioridazine and metabolites in serum were measured by HPLC. Slow hydroxylators of debrisoquin obtained higher serum levels of thioridazine with a 2.4-fold higher Cmax and a 4.5-fold larger AUC(0-infinity) associated with a twofold longer half-life compared with that of rapid hydroxylators. The side-chain sulphoxide (mesoridazine) and sulphone (sulphoridazine), which are active metabolites, appeared more slowly in serum and had lower Cmax values, but comparable AUC. The thioridazine ring-sulphoxide attained higher Cmax and 3.3-fold higher AUC in slow hydroxylators than in rapid hydroxylators of debrisoquin. Thus the formation of mesoridazine from thioridazine and the 4-hydroxylation of debrisoquin seem to be catalyzed by the same enzyme, whereas the formation of thioridazine ring-sulphoxide is probably formed mainly by another enzyme.

Adult↗
PubMed2002

The safety and pharmacokinetics of quetiapine when coadministered with haloperidol, risperidone, or thioridazine.

The effects of haloperidol, risperidone, and thioridazine on the pharmacokinetics and side-effect profile of quetiapine were investigated in 36 patients with schizophrenia, schizoaffective disorder, or bipolar disorder in a single-center, two-period, multiple-dose, open-label, randomized trial. Over a one-to two-week period, quetiapine doses were escalated to 300 mg twice daily (bid). Patients were then treated for at least 7 days at the target quetiapine dose and subsequently entered into the combination therapy period, receiving haloperidol (7.5 mg, bid), risperidone (3 mg, bid), or thioridazine (200 mg, bid) for 8.5 days (after 3 days of dose escalation). Key assessments included the pharmacokinetics of quetiapine at steady state (area under the curve within a dosing interval [AUCtSS], maximum [CmaxSS], and minimum [CminSS] observed plasma concentrations, and oral clearance [Cl/f]), as well as the UKU Side Effect Rating Scale scores and safety evaluations. Neither risperidone nor haloperidol had significant effects on quetiapine pharmacokinetics. However, thioridazine produced statistically significant changes, decreasing the least squares means values of the AUCtSS, CmaxSS, and CminSS by 40%, 47%, and 31%, respectively, and increasing Cl/f by 68%. Increases in the following adverse events were noted during coadministration: somnolence (risperidone), insomnia and dry mouth (all three coadministered therapies), and dizziness (thioridazine). UKU side effect items that became worse in >or= 25% of patients during each coadministration period included sedation and increased sleep duration. Results of laboratory tests, electrocardiograms, and vital sign measurements revealed few clinically important changes. Clinical stability can be maintained with good tolerability during the transition from quetiapine monotherapy to periods of coadministration with haloperidol, risperidone, or thioridazine. Coadministration of either haloperidol or risperidone did not have any important effects on the steady-state pharmacokinetics of quetiapine. Thioridazine significantly increased the oral clearance of quetiapine. Increased doses of quetiapine may be necessary to control psychotic symptoms when thioridazine is coadministered with quetiapine.

Adolescent↗
PubMed2002

QTc interval lengthening is related to CYP2D6 hydroxylation capacity and plasma concentration of thioridazine in patients.

Thioridazine cardiotoxicity has been associated with a prolonged heart-rate corrected QT (QTc) interval. However, no systematic studies have been performed on patients at therapeutic doses. The present study aimed to evaluate the influence of dose and plasma concentration of thioridazine and CYP2D6 enzyme status on the QTc interval in psychiatric patients. Sixty-five Spanish European psychiatric patients receiving thioridazine antipsychotic monotherapy were studied. The plasma levels of thioridazine and its metabolites were determined by high-performance liquid chromatography. All patients were phenotyped for CYP2D6 activity with debrisoquine during treatment. Thirty-five patients (54%) had a QTc interval over 420 ms. The lengthening of QTc interval was correlated with plasma concentration (p < 0.05) and daily dose (p < 0.05) of thioridazine. CYP2D6 enzyme hydroxylation capacity, evaluated by debrisoquine metabolic ratio (MR) (p < 0.05) and thioridazine/mesoridazine ratio (p < 0.05), was also correlated with QTc intervals. The present study shows the relationship between QTc interval lengthening among psychiatric patients treated at therapeutical doses with the dose and the plasma concentration of thioridazine. Since debrisoquine MR has been shown to be correlated with the QTc intervals, CYP2D6 enzyme hydroxylation capacity might be relevant in determining the risk for QTc interval lengthening. Patients with impaired CYP2D6 enzyme activity due to enzyme inhibition by thioridazine might be more prone to increased risk of sudden death due to torsade de pointes type cardiac dysrhythmia.

Adrenergic Agents↗
PubMedDate not supplied

Thioridazine induces immediate and delayed erythema in photopatch test.

Thioridazine is a phenothiazine derivative that has been used as an antipsychotic; it rarely causes photosensitization. However, we noticed that this drug induced an erythematous reaction in a photopatch test. Six volunteers were patch tested with various concentrations of thioridazine and irradiated with a range of UVA doses, and the time courses of the color of and blood flow to the test sites were monitored. The free-radical metabolites of thioridazine generated under UVA irradiation and its effects on ascorbate radical formation were examined with an electron paramagnetic resonance (EPR) spectrometer in vitro. As a result, immediate erythema developed during UVA irradiation in most subjects when 1% thioridazine was applied for 48 h and irradiation doses were higher than 4 J cm(-2). Another peak of erythematous reaction was observed 8-12 h after irradiation. The in vitro examination detected an apparent EPR signal, which appeared when 2 mM thioridazine in air-saturated phosphate buffer was irradiated with UVA, whereas this reaction was attenuated under anaerobic conditions. The EPR signal of the ascorbate radical was augmented under both aerobic and anaerobic conditions. Thioridazine-derived oxidants and/or thioridazine radicals generated during UVA irradiation seem to play an important role in this unique phototoxic reaction.

Adult↗
PubMed1980

Effect of thioridazine on the first-pass kinetics of [14C]imipramine in perfused rat liver: interaction at hepatic binding sites.

1. The effect of thioridazine on the first-pass removal and hepatic metabolism of [14C]imipramine was examined in a single-pass rat liver perfusion system using a perfusate free of drug-binding components. Drug exposure continued for 45 min, and bile was collected and analysed during the final 15 min when approx. steady-state conditions were attained. 2. Thioridazine decreased the hepatic extraction ratio for imipramine, lowered the hepatic concentration (P < 0.1) and increased the effluent perfusate-to-liver ratios of imipramine. It is suggested that the increased imipramine in the effluent perfusate was due to competition of thioridazine for non-metabolizing binding sites in the liver rather than to inhibition of drug metabolism. 3. Thioridazine markedly increased desipramine concentrations in both liver and effluent perfusate. This may have resulted from decreased hepatic binding of imipramine, which made more free drug available for demthylation. Competition with thioridazine for hepatic binding sites also explains the increased diffusion of desipramine into the effluent perfusate. 4. Lower concentrations of 2-hydroxylated metabolites, especially 2-hydroxyimipramine, were found in bile when thioridazine was administered with imipramine. There was no evidence of inhibition of imipramine 2-hydroxylation. From bile-to-liver ratios, it is suggested that thioridazine and/or its metabolites inhibits glucuronylation of 2-hydroxyimipramine but not of 2-hydroxydesipramine.

Animals↗
PubMedDate not supplied

Effects of selective cytochrome P-450 inhibitors on the metabolism of thioridazine. In vitro studies.

The aim of the present study was to determine optimum conditions for the study of thioridazine metabolism in rat liver microsomes and to investigate the influence of specific cytochrome P-450 inhibitors on 2- and 5-sulfoxidation, and N-demethylation of thioridazine. Basing on the developed method, the thioridazine metabolism in liver microsomes was studied at linear dependence of the product formation on time, and protein and substrate concentrations (incubation time was 15 min, concentration of microsomal protein was 0.5 mg/ml, substrate concentrations were 25, 50 and 75 nmol/ml). Dixon analysis of tioridazine metabolism carried out in the control liver microsomes, in the absence and presence of specific cytochrome P-450 inhibitors, showed that quinine (CYP2D1 inhibitor), metyrapone (CYP2B1/B2 inhibitor) and alpha-naphthoflavone (CYP1A2 inhibitor) affected while erythromycin (CYP3A inhibitor) and sulfaphenazole (CYP2C9 inhibitor) did not affect the neuroleptic biotransformation. Thus, quinine and metyrapone inhibited competitively thioridazine N-demethylation and mono-2-sulfoxidation. As reflected by Ki values, N-demethylation was inhibited to a higher degree (Ki = 16.5 and 43 microM, respectively) than mono-2-sulfoxidation (Ki = 25 and 137 microM, respectively). On the other hand, alpha-naphthoflavone inhibited competitively not only N-demethylation and mono-2-sulfoxidation, but also 5-sulfoxidation of thioridazine. The calculated Ki values showed that the highest potency of alpha-naphthoflavone to inhibit thioridazine metabolism was observed for N-demethylation and it descended in the following order: N-demethylation (Ki = 13.8 microM) > mono-2-sulfoxidation (Ki = 34 microM) > 5-sulfoxidation (Ki = 70.4 microM). In conclusion, it can be assumed that N-demethylation and mono-2-sulfoxidation are catalyzed by the isoenzymes 2D1, 2B and 1A2 while 5-sulfoxidation only by 1A2; isoenzymes belonging to the subfamilies 2C and 3A seem not to be involved in the metabolism of thioridazine. The obtained results are discussed in the view of species and structure differences in the enzymatic catalysis of phenothiazines' metabolism as well as in relation to their pharmacological and clinical significance.

Animals↗
PubMed1975

Comparative symptomatological and evoked potential studies with d-amphetamine, thioridazine, and placebo in hyperkinetic children.

In a double-blind study, 62 hyperkinetic children were randomly assigned to 8 weeks of treatment with either placebo, thioridazine, or d-amphetamine. The overall clinical symptomatology improved with all three substances, although d-amphetamine was significantly superior to placebo and thioridazine. Out of eight symptom clusters rated by the parents, two improved significantly with placebo, one with thioridazine, and six with d-amphetamine. The d-amphetamine was superior to placebo in reducing muscular tension and superior to thioridazine in decreasing hyperactive-impulsive behavior, psychosomatic problems, and muscular tension. Out of four teachers' symptom clusters, inattentive-passive behavior was significantly improved by thioridazine (which was also superior to placebo), while hyperactivity was reduced by d-amphetamine. Quantitative evaluation of visual evoked potentials (VEPs) revealed an increase in latencies and decrease in amplitudes during thioridazine treatment. Paradoxically, d-amphetamine also increased latencies, while tending to augment amplitudes. Regression and correlation analysis of clinical symptomatology with VEP variables showed that the shorter the pretreatment latencies and the higher the amplitudes, the more disturbed was the child. Short latencies and small amplitudes in the pretreatment period were predictors of good therapeutic outcome with subsequent thioridazine treatment, while short latencies and high amplitudes were indicative of such with d-amphetamine treatment. During therapy, the greater the drug-induced augmentation of latencies, the greater the clinical improvement. Finally, VEP differences between therapy-responsive and -resistant patients were explored and discussed.

Administration, Oral↗
PubMed1984

Greater potency of mesoridazine and sulforidazine compared with the parent compound, thioridazine, on striatal dopamine autoreceptors.

The electrically evoked overflow of dopamine (DA) from perfused rabbit striatal slices was used to assess the relative functional potencies of thioridazine, a phenothiazine antipsychotic agent, and two of its major metabolites, mesoridazine (thioridazine-2-sulfoxide) and sulforidazine (thioridazine-2-sulfone). Thioridazine (1000 nM) enhanced the electrically evoked overflow of DA by 18.3 +/- 4.6% (n = 4) at 0.3 Hz. Mesoridazine and sulforidazine likewise produced only small increases (5-20%) in evoked overflow of DA from slices stimulated at 0.3 Hz. At this frequency of stimulation, apomorphine (30 nM) inhibited the overflow of DA by 71.4 +/- 8.43% (n = 40). All three drugs antagonized, in a concentration-dependent fashion, the inhibitory effect of apomorphine (30 nM) on electrically evoked DA release at 0.3 Hz. The IC50 for thioridazine for antagonizing the effect of apomorphine was 130 nM, whereas that for mesoridazine was 14.4 nM and for sulforidazine was 6.1 nM. These results indicate that thioridazine and its two clinically active metabolites can block striatal DA autoreceptors involved in modulating DA release. The observation that mesoridazine and sulforidazine were significantly more potent than the parent drug is consistent with the hypothesis that a major part of the pharmacologic responses to thioridazine may be a consequence of its metabolism to active compounds.

Animals↗
PubMed2006

hERG K+ channel blockade by the antipsychotic drug thioridazine: An obligatory role for the S6 helix residue F656.

The phenothiazine antipsychotic agent thioridazine has been linked with prolongation of the QT interval on the electrocardiogram, ventricular arrhythmias, and sudden death. Although thioridazine is known to inhibit cardiac hERG K(+) channels there is little mechanistic information on this action. We have investigated in detail hERG K(+) channel current (I(hERG)) blockade by thioridazine and identified a key molecular determinant of blockade. Whole-cell I(hERG) measurements were made at 37 degrees C from human embryonic kidney (HEK-293) cells expressing wild-type and mutant hERG channels. Thioridazine inhibited I(hERG) tails at -40mV following a 2s depolarization to +20mV with an IC(50) value of 80nM. Comparable levels of I(hERG) inhibition were seen with physiological command waveforms (ventricular and Purkinje fibre action potentials). Thioridazine block of I(hERG) was only weakly voltage-dependent, though the time dependence of I(hERG) inhibition indicated contingency of blockade upon channel gating. The S6 helix point mutation F656A almost completely abolished, and the Y652A mutation partially attenuated, I(hERG) inhibition by thioridazine. In summary, thioridazine is one of the most potent hERG K(+) channel blockers amongst antipsychotics, exhibiting characteristics of a preferential open/activated channel blocker and binding at a high affinity site in the hERG channel pore.

Antipsychotic Agents↗
PubMed1984

Red blood cell and plasma levels of thioridazine and mesoridazine in schizophrenic patients.

Thioridazine and mesoridazine levels and levels of thioridazine plus metabolites were determined in plasma and red blood cells (RBC) by gas-liquid chromatography (GLC) and spectrofluorometry (SP), respectively, in schizophrenic patients treated with fixed doses of thioridazine. There was wide interpatient variability in RBC:plasma ratios for thioridazine and mesoridazine, a higher ratio of thioridazine to mesoridazine in RBC than plasma, and a higher ratio of GLC total (thioridazine plus mesoridazine), to SP-determined total drug constituents in RBC than in plasma. RBC showed a monotonic increase in drug levels with dose, whereas levels of drug in the plasma began to level off above the 250 mg/day dose. Drug levels 24 h after the acute dose did not predict steady-state blood levels in plasma or RBC.

Adolescent↗
PubMed1977

Plasma levels and half lives of thioridazine and some of its metabolites. II. Low doses in older psychiatric patients.

Plasma-levels of thioridazine, mesoridazine, sulphoridazine and two other metabolites were determined in ten older chronic psychotic patients on thioridazine therapy. The plasma-level before the morning dose of thioridazine was the most reliable parameter for clinical studies. An intra-individual relationship between lower doses of thioridazine and plasma-levels was found. The percentage contribution of psychoactive compounds to the total sum of "thioridazine plus metabolites" ranged from 43-74%. The mean "early disappearance half-life" of thioridazine was 5 hours, and its mean "late disappearance half-life" was 26 hours.

Aged↗