The interaction between i.v. theophylline and chronic oral dosing with slow release nifedipine in volunteers.

Jackson, S. H. D.; Shah, K.; Debbas, Nadia; Johnston, Atholl; Peverel-Cooper, C. A.; Turner, Paul

doi:10.1111/j.1365-2125.1986.tb05212.x

Cited by 17 publications

(4 citation statements)

References 12 publications

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“…Although small, these changes were statistically significant due to the power of the study. The present data are consistent with previous reports which found no change in theophylline disposition with nifedipine treatment of asthmatic subjects (Jackson et al, 1986;Garty et al, 1986). Further, our study shows that nifedipine has little effect on the individual pathways for theophylline metabolism.…”

Section: Discussionsupporting

confidence: 93%

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

Robson

Miners

Birkett

1988

Brit J Clinical Pharma

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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.

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Section: Discussionsupporting

confidence: 93%

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

Robson

Miners

Birkett

1988

Brit J Clinical Pharma

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“…In a study evaluating ketolytic and glycolytic enzyme expression in 22 malignant glioma biopsies, the rate limiting mitochondrial ketolytic enzymes were low or very low in 14 of 17 GBMs and in 1 of 5 anaplastic gliomas, while at least one glycolytic enzyme was overexpressed in 13 of 17 GBMs and all 5 anaplastic gliomas [144]. Another study involving 5 different glioma cell lines concluded that glioma cells are unable to metabolize βHB to compensate for glucose restriction like healthy brain cells, even when ketolytic enzymes were expressed [142,143].…”

Section: In Vitro Studies In Gliomasmentioning

confidence: 99%

Targeting the Warburg effect for cancer treatment: Ketogenic diets for management of glioma

Poff

Koutnik

Egan

et al. 2019

Seminars in Cancer Biology

146

119

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Gliomas are a highly heterogeneous tumor, refractory to treatment and the most frequently diagnosed primary brain tumor. Although the current WHO grading system (2016) demonstrates promise towards identifying novel treatment modalities and better prediction of prognosis over time, to date, existing targeted and mono therapy approaches have failed to elicit a robust impact on disease progression and patient survival. It is possible that tumor heterogeneity as well as specifically targeted agents fail because redundant molecular pathways in the tumor make it refractory to such approaches. Additionally, the underlying metabolic pathology, which is significantly altered during neoplastic transformation and tumor progression, is unaccounted for. With several molecular and metabolic pathways implicated in the carcinogenesis of CNS tumors, including glioma, we postulate that a systemic, broad spectrum approach to produce robust targeting of relevant and multiple molecular and metabolic regulation of growth and survival pathways, critical to the modulation of hallmarks of carcinogenesis, without clinically limiting toxicity, may provide a more sustained impact on clinical outcomes compared to the modalities of treatment evaluated to date. The objective of this review is to examine the emerging hallmark of reprogramming energy metabolism of the tumor cells and the tumor microenvironment during carcinogenesis, and to provide a rationale for exploiting this hallmark and its biological capabilities as a target for secondary chemoprevention and treatment of glioma. This review will primarily focus on interventions to induce ketosis to target the glycolytic phenotype of many cancers, with specific application to secondary chemoprevention of low grade glioma- to halt the progression of lower grade tumors to more aggressive subtypes, as evidenced by reduction in validated intermediate endpoints of disease progression including clinical symptoms.

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“…Eight healthy volunteers (four males) aged 21-34 years and weighing 52-86 kg received slow release nifedipine at a dose of 20 mg, 12 hourly for a total of six doses (up to and including 09.00 h on day 4) as part of a theophylline/nifedipine interaction study (Jackson et al, 1986). On the day of the study, starting at 09.00 h, blood samples were taken at 0, 10, 20, 40 min, 1, 1.5, 2, 3, 4, 6, 8, and 12 h after dosing for determination of serum nifedipine concentrations.…”

Section: Methodsmentioning

confidence: 99%

The bioavailability and pharmacokinetics of slow release nifedipine during chronic dosing in volunteers.

Debbas¹,

Jackson²,

Shah³

et al. 1986

Brit J Clinical Pharma

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Eight healthy volunteers received slow release nifedipine 20 mg 12 hourly, for six doses. A nifedipine pharmacokinetic profile was performed after the fifth dosing interval using 12 sampling times over 12 h. A specific high pressure liquid chromatography (h.p.l.c.) nifedipine assay was used. Six of the volunteers subsequently received an i.v. infusion of 3.5 mg of nifedipine after an identical period (five dosing intervals) of chronic oral dosing with slow release nifedipine 20 mg 12 hourly. An identical pharmacokinetic profile was performed after the infusion. Bioavailability, clearance (CL), apparent volume of distribution (V), apparent half life (t1/2) and area under the curve (AUC) were calculated. The geometric mean apparent t1/2 for the slow release preparation was 6.3 +/‐ 2.0 h. In the six volunteers, the mean bioavailability was 46% (range 29‐86%), the mean CL was 588.0 +/‐ 67.1 ml min‐1, the mean apparent V was 160.1 +/‐ 61.7 l. The pharmacokinetics of slow release nifedipine during chronic dosing appear similar to those derived from single dose studies.

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The interaction between i.v. theophylline and chronic oral dosing with slow release nifedipine in volunteers.

Cited by 17 publications

References 12 publications

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

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

Targeting the Warburg effect for cancer treatment: Ketogenic diets for management of glioma

The bioavailability and pharmacokinetics of slow release nifedipine during chronic dosing in volunteers.

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