Pharmacokinetics of Red Blood Cell Phenothiazine and Clinical Effects

Garver, David L.; Davis, John M.; Dekirmenjian, H.; Jones, Frank; Casper, Regina C.; Haraszti, Joseph

doi:10.1001/archpsyc.1976.01770070092011

Cited by 43 publications

(3 citation statements)

References 6 publications

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“…Dystonic reactions to the neuroleptic butaperazine in adult schizophrenics occurred 23 h or more after a single oral dose (Garver etal., 1978), and the elimination half-life in patients who suffered this effect were reported to be longer than in those who did not (Garver et al (1976). Furthermore, the red blood cell concentrations of butaperazine were significantly higher at the time of dystonia in the patients who suffered this effect than at the same time points in those who did not.…”

Section: Discussionmentioning

confidence: 91%

Dystonic reactions and the pharmacokinetics of metoclopramide in children.

Bateman¹,

Craft²,

Nicholson³

et al. 1983

Brit J Clinical Pharma

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Newcastle upon Tyne, NE1 7RUThe pharmacokinetics of metoclopramide have been studied in nine children receiving the drug as prophylaxis for cytotoxic induced vomiting. Plasma concentrations of metoclopramide have also been studied in three children with dystonic reactions to the drug. The pharmacokinetics in children were similar to those reported in healthy adults. There was no difference in the plasma concentration of metoclopramide of children with dystonia when compared to those without this adverse effect. Kinetic differences in childhood do not explain the occurrence of dystonia, which in the individual appears to be related to factors other than plasma drug concentrations.

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Section: Discussionmentioning

confidence: 91%

Dystonic reactions and the pharmacokinetics of metoclopramide in children.

Bateman¹,

Craft²,

Nicholson³

et al. 1983

Brit J Clinical Pharma

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“…Long term or permanent paralysis of the retractor penis muscle, although very rare, has been known to occur following acepromazine administration (Lucke & Sansom, 1979). This effect seems to be dose-related and appears to occur more frequently in stallions than geldings (Gibbs, 1978;Jones, 1979). For this reason it has been recommended that the use of acepromazine in valuable breeding stallions be kept to the minimum possible dosages and injected intramuscularly instead of i.v.…”

Section: Pharmacological Responsesmentioning

confidence: 99%

The pharmacokinetics, pharmacological responses and behavioral effects of acepromazine in the horse

Ballard

Shults

Kownacki

et al. 1982

Vet Pharm & Therapeutics

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After intravenous (i.v.) injection, acepromazine was distributed widely in the horse (Vd = 6.6 litres/kg) and bound extensively (greater than 99%) plasma proteins. Plasma levels of drug declined with an alpha half-life of 4.2 min, while the beta phase or elimination half-life was 184.8 min. At a dosage level of 0.3 mg/kg acepromazine was detectable in the plasma for 8 h post dosing. The whole blood partitioning of acepromazine was 46% in the plasma phase and 54% in the erythrocyte phase. Penile prolapse was clearly evident at doses from 0.01 mg/kg to 0.4 mg/kg i.v., and the duration and extent of protrusion were dose related. Hematocrit levels were significantly lowered by administration of 0.002 mg/kg i.v. (about 1 mg to a 500 kg horse) and increasing dosages resulted in greater than 20% lowering of the hematocrit from control levels. Pretreatment of horses with acepromazine also reduced the variable interval (VI 60) responding rate in all horses tested. These data show that hematocrit changes are the most sensitive pharmacological responses to acepromazine, followed by changes in penile extension, respiratory rate, VI responding and locomotor responses. Acepromazine is difficult to detect in plasma at normal clinical doses. However, because of its large volume of distribution, its urinary elimination is likely prolonged, and further work on its elimination in equine urine is required.

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“…The pharmacokinetic parameters of the subjects suffering dystonia were not different from those of the others and a pharmacodynamic explanation appears most appropriate. Garver et al (1976) observed a delayed dystonic reaction following intravenous butaperazine and attributed it to dopaminergic-cholinergic imbalance during the decline of plasma drug concentration when there was transient, relatively excessive dopaminergic activity. While an imbalance between dopaminergic and cholinergic neuronal pathways seems the most likely explanation, other neuronal pathways may be involved.…”

Section: Discussionmentioning

confidence: 99%

Clinical pharmacology of prochlorperazine in healthy young males.

Isah,

Rawlins,

Bateman

1991

Brit J Clinical Pharma

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1. The pharmacokinetics and pharmacodynamics of prochlorperazine (PCZ) have been studied in healthy young males following single 12.5 mg i.v. and 50 mg oral doses, and during repeated doses (25 mg twice daily) for 14 days. 2. Oral bioavailability was low and an N‐desmethyl metabolite was detected. Plasma clearance was high (0.98 1 kg‐1 h) and the volume of distribution was large (12.9 1 kg‐1) after i.v. dosing. 3. The terminal elimination half‐life of PCZ was 9 +/‐ 1 h and 8 +/‐ 2 h after i.v. and single oral dosing, respectively. The urinary recoveries of drug and metabolite were low. 4. Accumulation of PCZ and its metabolite occurred following repeated dosing. The half‐life at the end of 14 days therapy was 18 +/‐ 4 h. 5. Postural tachycardia, decreased salivary flow, impaired psychomotor function and a diminished level of arousal were observed after intravenous PCZ. Similar effects, but of lower magnitude were observed after single oral doses. During chronic dosing postural tachycardia and antihistaminic effects were observed, the latter not being observed after single doses. 6. After single intravenous dosing the maximal drug effects occurred 2‐4 h after peak plasma drug concentrations for all measures except for plasma prolactin and self‐scored restlessness 7. An antagonist action at dopamine (D2), muscarinic‐cholinergic and alpha‐adrenoceptors is postulated after single doses, with antihistaminic effects during chronic dosing, possibly indicating the presence of an active metabolite.

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Pharmacokinetics of Red Blood Cell Phenothiazine and Clinical Effects

Cited by 43 publications

References 6 publications

Dystonic reactions and the pharmacokinetics of metoclopramide in children.

Dystonic reactions and the pharmacokinetics of metoclopramide in children.

The pharmacokinetics, pharmacological responses and behavioral effects of acepromazine in the horse

Clinical pharmacology of prochlorperazine in healthy young males.

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