Human whole blood and parotid saliva concentrations of oral and intramuscular promethazine

Digregorio, G. John; Ruch, Eileen

doi:10.1002/jps.2600691234

Cited by 25 publications

(11 citation statements)

References 8 publications

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“…The renal clearance of PMZ was found to be low whilst that of its sulphoxide metabolite was considerably higher. The unbound fraction of PMZ in blood has been estimated as 0.22 (DiGregorio & Ruch, 1980). Using this estimate a mean corrected renal clearance of 26.7 ml min-' may be calculated.…”

Section: Discussionmentioning

confidence: 99%

“…Yet despite extensive application and a history of more than 30 years in clinical practice, little is known concerning its disposition in man. DiGregorio & Ruch (1980) reported maximum blood concentrations of 22 ng/ml after intramuscular dosing of 25 mg of PMZ suggesting a large volume of distribution. In the same study peak blood concentrations after oral dosing were only 25% of those following intramuscular administration and this was attributed to first-pass metabolism.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetics of promethazine and its sulphoxide metabolite after intravenous and oral administration to man.

Taylor¹,

Jb²,

Shaffer³

et al. 1983

Brit J Clinical Pharma

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1 Blood concentrations of promethazine and promethazine sulphoxide have been measured following oral and intravenous administration of promethazine to seven healthy male volunteers. 2 Promethazine disposition is characterised by a large volume of distribution (1970 1) and a high blood clearance (1.141 min-'). Less than 1% of the dose is excreted unchanged in the urine, therefore total body clearance is essentially metabolic clearance. In accord with this high clearance the oral availability of promethazine is only 25%. The absorption of promethazine from the gastrointestinal tract exceeds 80% in most subjects. Minimal metabolism by the gastrointestinal mucosa is implicated. 3 Promethazine sulphoxide pharmacokinetics are consistent with a pronounced first pass effect. Although the area under the curve for this metabolite is not route dependent, there is a marked alteration in the shape of the metabolite curve when oral and intravenous data are compared. Evidence is presented to support the hypothesis that S-oxidation of promethazine is predominantly an hepatic event. The conclusions of previous investigators with regard to the role of the gut mucosa in S-oxidation of phenothiazines is critically assessed.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of promethazine and its sulphoxide metabolite after intravenous and oral administration to man.

Taylor¹,

Jb²,

Shaffer³

et al. 1983

Brit J Clinical Pharma

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“…The obtained results are explained as follows: both drugs CPM and PMZ are characterized by considerable presystem metabolism (DiGregorio and Ruch, 1980;Kholodov and Yakovlev, 1985;American Hospital Formulary Service, 1991). They are captured by the liver at their first pass through it.…”

Section: Resultsmentioning

confidence: 96%

“…Chlorpromazine (CPM) is a strong neuroleptic, used also in antiepileptic therapy, whereas promethazine (PMZ) possesses antihistamine action and is also a neuroleptic (Mashkowsky, 2000). Both drugs, derivatives of phenothiazine, are characterized by strong presystem metabolism and surface activity (Florence, 1980;DiGregorio and Ruch, 1980;Kholodov and Yakovlev, 1985;American Hospital Formulary Service, 1991;Rukhadze et al, 2002). CPM and PMZ are used also simultaneously, viz.…”

Section: Introductionmentioning

confidence: 98%

Interaction of surface‐active drugs in rabbits

Rukhadze

Alexishvili

Gonashvili

et al. 2004

Biomedical Chromatography

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The interaction of chlorpromazine and promethazine in vivo has been investigated. The drugs were administered to the rabbit orally as a single dose (100 mg of each drug) as well as simultaneously with an interval of 15 min. The presence of multiple peaks at the separate administration of promethazine and chlorpromazine on the one hand, and increase of number of peaks, symbathic character of kinetic curves of mentioned drugs and its prolonged appearance in the systemic circulation of the blood by simultaneous administration on the other hand, may be explained by the intensive presystem metabolism and surface-activity ability of these drugs, and by the periodic 'lassitude' of liver for their capture and elimination (either presystem or systemic). The micelle formation from these drugs in the gastro-intestinal tract and formation of the mixed micelles on simultaneous administration were also taken into consideration. Chlorpromazine is more strongly captured by the liver at its first pass through it than promethazine, from comparison of pharmacokinetics of these drugs administered separately. Therefore, chlorpromazine on simultaneous administration occupies the sites of the liver which were covered by promethazine at single dose, thereby substituting promethazine and promoting its transferral into the systemic blood circulation. This results in a large increase in promethazine content in blood, additional peaks appear and the presence of promethazine in the blood is prolonged. The influence of chlorpromazine on the kinetics of promethazine is especially obvious when chlorpromazine enters the organism first and more easily occupies those sites in the liver which participate in the capture and elimination of both drugs. Concerning influence of promethazine on the kinetics of chlorpromazine, promethazine reinforces in some way the ability of liver to capture chlorpromazine, thereby intensifying the presystem metabolism of chlorpromazine and inhibiting its own metabolism. The analogous effect was observed in the study of the influence of promethazine on the kinetics of carbamazepine.

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“…18 Peak plasma concentrations occur after 2 to 3 hours when promethazine is administered orally. [18][19][20][21] The elimination half life after oral administration is 12 to 15 hours. 22 Therefore, we decided to administer the medication 2 hours before treatment.…”

Section: Discussionmentioning

confidence: 99%