Pharmacokinetic interactions between phenylpropanolamine, caffeine and chlorpheniramine in rats

Kaddoumi, Amal; Nakashima, Mihoko N.; Wada, Mitsuhiro; Nakashima, Kenichiro

doi:10.1016/j.ejps.2004.03.007

Cited by 10 publications

(6 citation statements)

References 27 publications

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“…Like verapamil, caffeine when simultaneously exists with a P-gp substrate it acts as inhibitor of P-gp increasing the P-gp substrate intracellular uptake. In addition, Kaddoumi et al reported the possible role of caffeine as a P-gp inhibitor at the rat BBB when combined with phenylpropanolamine (PPA) (39). Under these conditions, treatment with caffeine caused an increase in PPA levels in the rat brain.…”

Section: Discussionmentioning

confidence: 99%

Exposure of LS-180 Cells to Drugs of Diverse Physicochemical and Therapeutic Properties Up-regulates P-glycoprotein Expression and Activity

Abuznait

Patrick²,

Kaddoumi

2011

J Pharm Pharm Sci

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Purpose Drug transporters are increasingly recognized as important determinants of variability in drug disposition and therapeutic response, both in pre-clinical and clinical stages of drug development process. The role P-glycoprotein (P-gp) plays in drug interactions via its inhibition is well established. However, much less knowledge is available about drugs effect on P-gp up-regulation. The objective of this work was to in vitro investigate and rank commonly used drugs according to their potencies to up-regulate P-gp activity utilizing the same experimental conditions. Methods The in vitro potencies of several drugs of diverse physicochemical and therapeutic properties including rifampicin, dexamethasone, caffeine, verapamil, pentylenetetrazole, hyperforin, and β-estradiol over broad concentration range to up-regulate P-gp expression and activity were examined. For dose-response studies, LS-180 cells were treated with different concentrations of the selected drugs followed by P-gp protein and gene expressions analyses. P-gp functionality was determined by uptake studies with rhodamine 123 as a P-gp substrate, followed by Emax/EC50 evaluation. Results The results demonstrated a dose-dependent increase in P-gp expression and activity following treatments. At 50 μM concentration (hyperforin, 0.1 μM), examined drugs increased P-gp protein and gene expressions by up to 5.5 and 6.2-fold, respectively, while enhanced P-gp activity by 1.8–4-fold. The rank order of these drugs potencies to up-regulate P-gp activity was as following: hyperforin ⋙ dexamethasone ≈ β-estradiol > caffeine > rifampicin ≈ pentylenetetrazole > verapamil. Conclusions These drugs have the potential to be involved in drug interactions when administered with other drugs that are P-gp substrates. Further studies are needed to in vivo evaluate these drugs and verify the consequences of such induction on P-gp activity for in vitro-in vivo correlation purposes.

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Section: Discussionmentioning

confidence: 99%

Exposure of LS-180 Cells to Drugs of Diverse Physicochemical and Therapeutic Properties Up-regulates P-glycoprotein Expression and Activity

Abuznait

Patrick²,

Kaddoumi

2011

J Pharm Pharm Sci

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“…3) . In a previous study the possibility of a pharmacokinetic interaction of PPA with caffeine and CPR was investigated and the results of this study suggest that caffeine and CPR, either separately or in combination, significantly alter the pharmacokinetic parameters of PPA in brain (Kaddoumi et al, 2004). As in the literature, the pharmacokinetics of cold drugs may be altered by using other drugs in the treatment of the common cold when given in combination.…”

Section: Discussionmentioning

confidence: 82%

“…Most of the scientific literature reports major interferences between ascorbic acid and/or CPR, APAP, PPA with a great number of chemical species, in a variety of matrices. For this reason, considerable attention has been focused on drug-drug interaction in recent years (Sawamoto et al, 1997;http://www.nlm.nih.gov;Koytchev et al, 2003;Mitra et al, 1991;Miller and Jollow, 1984;Dilon et al, 2004;Kaddoumi et al, 2004;Yigit et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the efficacy of 99mTc-labeled ascorbic acid on common cold–cough drugs in rats

et al. 2007

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Multiple-drug therapy is common in current clinical practice. Because of this, people have been ready to embrace simplistic approaches to cold treatment, such as vitamin C and zinc. Ascorbic acid (vitamin C) is mostly administrated together with cough-cold drugs. The aim of this study was to investigate the effect of cough-cold drugs on the uptake of ascorbic acid using 99m Tc-ascorbic acid ( 99m Tc-AA) in male albino Wistar rats. Ascorbic acid was labeled with Tc-99m and the distribution of 99m Tc-AA was investigated. The uptake of 99m Tc-AA was evaluated when administrated alone (group I), with chlorpheniramine maleate (CPR) (group II), with phenylpropanolamine hydrochloride (PPA) (group III), and with acetaminophen (APAP) (group IV). In some organs (apart from kidneys, intestinal system, and stomach) the uptake of 99m Tc-AA was not significantly affected by the administration of 99m Tc with CPR or 99m Tc with APAP at 120 min. On the other hand, there was significant difference in the uptake of 99m Tc-AA between groups I and III. The administration of 99m Tc-AA with PPA in rats caused an increase of the uptake of 99m Tc-AA at 120 min in the investigated organs compared to the administration of 99m Tc-AA alone. The present data show that vitamin C might be more effective for the treatment of common cold when coadministered with PPA compared to with CPR, with APAP, or alone.

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“…Our results showed that the observed adverse effects associated with PPA use could be related to the significant increase in its levels in the brain. 72 These results revealed the importance of monitoring of pharmacokinetic parameters in target tissue in addition to these in blood to evaluate the pharmacokinetic drug-drug interactions.…”

Section: ·2 Evaluation Of Drug-drug Interaction Potential Formentioning

confidence: 99%

“…In our study, the combination of HPLC separation with fluorescence detection using our original labeling reagent (DIBCl) and microdialysis sampling were used for estimation for drug-drug interactions of abusable drugs. 58,[70][71][72] MDMA tablets often contain other active components having hallucinogenic and/or stimulant effect such as caffeine, ketamine, ephedrine or methamphetamine. After administration of MDMA (5 mg/kg, i.p.)…”

Section: ·2 Evaluation Of Drug-drug Interaction Potential Formentioning

confidence: 99%

Analytical Studies on the Development of High-Performance Liquid Chromatographic Methods with Fluorescence or Chemiluminescence Detections and Their Practical Applications

2009

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This review describes a comprehensive investigation focusing on syntheses of analytical reagents, followed by their utilization in development of analytical methods, and leading to practical applications for rational use of medicaments centering on abused drugs. Many kinds of analytical reagents for fluorescence and chemiluminescence detections have been synthesized with the intention of improving sensitivity. By properly combining the developed analytical reagents with an HPLC separation technique, one could determine ultra-small amounts of abused drugs such as stimulants, narcotics and obesity drugs in various matrices. Furthermore, chiral analyses of some abused drugs and evaluation of their potential for drug-drug interaction were also performed. The developed methods might be useful for forensic and toxicological studies on drug abuse. Also, the results obtained in our study might contribute to the prediction of and the protection of human health from risks of abused drugs.

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Pharmacokinetic interactions between phenylpropanolamine, caffeine and chlorpheniramine in rats

Cited by 10 publications

References 27 publications

Exposure of LS-180 Cells to Drugs of Diverse Physicochemical and Therapeutic Properties Up-regulates P-glycoprotein Expression and Activity

Exposure of LS-180 Cells to Drugs of Diverse Physicochemical and Therapeutic Properties Up-regulates P-glycoprotein Expression and Activity

Evaluation of the efficacy of 99mTc-labeled ascorbic acid on common cold–cough drugs in rats

Analytical Studies on the Development of High-Performance Liquid Chromatographic Methods with Fluorescence or Chemiluminescence Detections and Their Practical Applications

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