The effect of oral verapamil therapy on antipyrine clearance.

Rumiantsev, D O; Piotrovskii, V. K.; Os, Riabokon'; Сластникова, И. Д.; Ev, Kokurina; Metelitsa, V I

doi:10.1111/j.1365-2125.1986.tb02942.x

Cited by 15 publications

(9 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Alternatively any inhibitory effect on parent drug metabolism may be offset by an increase in autoinduction during chronic CBZ therapy. Interestingly, VPA did not inhibit antipyrine metabolism significantly at relatively high concentrations of the drug unlike other enzyme inhibiting drugs that modify CBZ disposition, such as cimetidine (Macphee et al, 1984) and verapamil (Rumiantsev et al, 1986).…”

Section: Analysesmentioning

confidence: 91%

Effect of sodium valproate on carbamazepine disposition and psychomotor profile in man.

Macphee

Mitchell

Wiseman

et al. 1988

Brit J Clinical Pharma

View full text Add to dashboard Cite

1 The effect of sodium valproate (VPA; 500 mg thrice daily for 7 days) and matched placebo on the disposition and psychomotor profile of a single dose of carbamazepine (CBZ; 10 mg kg-1) was studied in eight healthy male subjects using a randomised balanced crossover design.2 VPA alone had no effect on antipyrine clearance, urinary 6p-hydroxycortisol excretion and a battery of psychomotor function tests after 3 days' treatment despite achieving a mean steady-state concentration (90 ± 6 mg 1-1) well within the target range (50-100 mg I-1) for the drug.3 VPA pre-treatment did not alter total CBZ area under the concentration-time curve (AUC 0-59 h) but did prolong CBZ elimination half life by 12% (P < 0.01). AUC 0-59 h for free plasma CBZ was 13% higher (P < 0.02) and half-life of unbound CBZ 16% longer (P < 0.02) during VPA treatment. CBZ-10, 11 epoxide (CBZ-E) levels (52%) and CBZ-E/ CBZ ratios (45%) were both elevated by concurrent VPA (P < 0.05) and free CBZ fraction was increased by 7% (P < 0.02). 4 The sole effect of VPA on the psychomotor profile of CBZ was prolongation of card sorting time (P < 0.05), although CBZ-related side effects were reported as more severe when VPA was also taken (P < 0.01). 5 These data suggest that VPA displaces CBZ from plasma protein binding sites and inhibits the metabolism of both the parent drug and its epoxide. The effect of VPA on the psychomotor profile of a large single dose of CBZ was minimal. 6 Further studies in epileptic patients receiving both these anticonvulsant drugs are warranted to appraise the extent and clinical relevance of their interaction.

show abstract

Section: Analysesmentioning

confidence: 91%

Effect of sodium valproate on carbamazepine disposition and psychomotor profile in man.

Macphee

Mitchell

Wiseman

et al. 1988

Brit J Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…Verapamil has been shown to increase the steady-state accumulation of CQ by CQ-resistant P. falciparum, and it was suggested that this effect was due to the inhibition of CQ efflux (18 The question remains as to whether the reversal of resistance produced by verapamil is related in any way to the mechanism involved with cimetidine. It is noteworthy that verapamil as well as cimetidine and metyrapone has been shown to be an inhibitor of the cyt P-450 superfamily of enzymes (22,24,30). These inhibitors are all selective for the isozymes of cyt P450 that they inhibit (3), a fact that raises the possibility that the differences observed in the modulatory effects of the drugs tested may reflect differences in the relative affinities of specific isozymes of cyt P450: i.e., Km for verapamil c that for cimetidine <<< that for metyrapone.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of drug susceptibility in Plasmodium falciparum in vitro and Plasmodium berghei in vivo by mixed-function oxidase inhibitors

Ndifor

Howells

Bray

et al. 1993

Antimicrob Agents Chemother

View full text Add to dashboard Cite

A number of compounds, as exemplified by verapamil and desipramine, have been shown to enhance the susceptibility of resistant malaria parasites to chloroquine. The mechanism by which these agents reverse resistance is still controversial but is thought to involve alterations in drug transport causing an increase in steady-state drug concentrations. We have proposed that an alternative resistance mechanism may involve the metabolic deactivation of the drug in some resistant parasites via cytochrome P-450 mixed-function oxidases.If the hypothesis is true, it should be possible to alter drug susceptibility in malaria parasites by the use of agents known to inhibit or induce cytochrome P-450 activities. We have assessed the ability of known inhibitors of cytochrome P-450 enzymes (cimetidine, metyrapone, and at-naphthoflavone) to enhance chloroquine susceptibility in Plasmodiumfalciparum culture-adapted and wild-type isolates in vitro and P. berghei in vivo.In all three systems, the inhibitor cimetidine enhanced parasite susceptibility to chloroquine, and this increase in susceptibility was unrelated to changes in chloroquine steady-state concentrations in vitro or to alterations in host pharmacokinetics in vivo. Additionally, the cytochrome P-450 inducer phenobarbital produced slight decreases in P. falciparum drug susceptibility in vitro. We have compared the ability of the cytochrome P-450 inhibitors cimetidine and metyrapone to enhance drug susceptibility with that of verapamil by using wild-type malaria isolates obtained from Cameroon. Verapamil completely reversed resistance, i.e., to below the cutoff point of 70 nM, in all the resistant isolates. Cimetidine enhanced chloroquine susceptibility in 60% of the isolates and reduced 50%o inhibitory concentrations by at least 43% in all the resistant isolates. The compounds tested had little or no effect on the 50%o inhibitory concentrations for the susceptible isolates. The data support a possible role for detoxification in chloroquine resistance, and even in the absence of such a process we have observed apparent chemosensitization by agents whose common biological feature is the inhibition of cytochrome P-450 enzymes. Additionally, sensitization has been observed in wild-type isolates of P. fakciparum obtained from immune residents of an area of endemicity as well as culture-adapted parasites.The malaria status in most areas of the world in which malaria is endemic has failed to improve over the last decade, despite predictions and speculations to the contrary, particularly those fuelled by hopes of a vaccine remedy. Resistance to antimalarial drugs has become a progressive and persistent obstacle to chemotherapy. Chloroquine (CQ) resistance, in particular, has continued to spread quite dramatically, while knowledge of the mechanism of development of resistance to this drug still eludes researchers (36).CQ resistance has now been reported in almost all subSaharan African countries and is firmly established in a large number of them (8), placing a considerable bur...

show abstract

“…Verapamil has been demonstrated to inhibit the clearances of antipyrine (Bauer et al, 1986;Rumiantsev et al, 1986) and carbamazepine (Macphee et al, 1986) in man. A case report suggests that verapamil may also inhibit theophylline clearance (Burnakis et al, 1983).…”

Section: Introductionmentioning

confidence: 99%

Selective inhibitory effects of nifedipine and verapamil on oxidative metabolism: effects on theophylline.

Robson

Miners

Birkett

1988

Brit J Clinical Pharma

View full text Add to dashboard Cite

Nine healthy male volunteers were studied to assess the possibility of an interaction between theophylline and nifedipine or verapamil using axrandomised, crossover design. Subjects received theophylline 125 mg 8 hourly with and without nifedipine 20 mg 12 hourly and verapamil 80 mg 8 hourly. Nifedipine treatment reduced mean total theophylline clearance by 9%, due to decreased clearances via 1-and 3-demethylation. Verapamil treatment reduced mean total theophylline clearance by 14%, due to decreased clearances via 1-and 3-demethylation and 8-hydroxylation. Verapamil and nifedipine at usual clinical doses are unlikely to cause clinically significant changes in theophylline disposition.

show abstract

The effect of oral verapamil therapy on antipyrine clearance.

Cited by 15 publications

References 19 publications

Effect of sodium valproate on carbamazepine disposition and psychomotor profile in man.

Effect of sodium valproate on carbamazepine disposition and psychomotor profile in man.

Enhancement of drug susceptibility in Plasmodium falciparum in vitro and Plasmodium berghei in vivo by mixed-function oxidase inhibitors

Selective inhibitory effects of nifedipine and verapamil on oxidative metabolism: effects on theophylline.

Contact Info

Product

Resources

About