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      Effects of tomato juice on the pharmacokinetics of CYP3A4-substrate drugs

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          We previously demonstrated that tomato juice (TJ) contains potent mechanism-based inhibitor(s) of CYP3A4. In this study, we investigated the effects of TJ and grapefruit juice (GFJ) on the pharmacokinetics of the CYP3A4-substrate drugs, nifedipine (NFP) and midazolam (MDZ), in male Wistar rats. Oral administration of GFJ 90 min before the intraduodenal administration of NFP or MDZ increased the area under the concentration–time curves (AUCs) of NFP and MDZ by 32.4% and 89.4%, respectively. TJ increased MDZ blood concentrations and AUC after intraduodenal MDZ administration; however, it had no effect on NFP. When MDZ and NFP were intravenously administered, GFJ significantly increased the AUC of MDZ, but only slightly increased that of NFP. In contrast, TJ only slightly increased the AUC of MDZ. These results suggest that, similar to GFJ, TJ influences the pharmacokinetics of CYP3A4-substrate drugs; however, it may be a drug-dependent partial effect.

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          A prospective study of tomato products, lycopene, and prostate cancer risk.

          Jonathan W. Willett, Meir J. Stampfer, Yan Liu … (2002)
          Some data, including our findings from the Health Professionals Follow-Up Study (HPFS) from 1986 through January 31, 1992, suggest that frequent intake of tomato products or lycopene, a carotenoid from tomatoes, is associated with reduced risk of prostate cancer. Overall, however, the data are inconclusive. We evaluated additional data from the HPFS to determine if the association would persist. We ascertained prostate cancer cases from 1986 through January 31, 1998, among 47 365 HPFS participants who completed dietary questionnaires in 1986, 1990, and 1994. We used pooled logistic regression to compute multivariate relative risks (RR) and 95% confidence intervals (CIs). All statistical tests were two-sided. From 1986 through January 31, 1998, 2481 men in the study developed prostate cancer. Results for the period from 1992 through 1998 confirmed our previous findings---that frequent tomato or lycopene intake was associated with a reduced risk of prostate cancer. Similarly, for the entire period of 1986 through 1998, using the cumulative average of the three dietary questionnaires, lycopene intake was associated with reduced risk of prostate cancer (RR for high versus low quintiles = 0.84; 95% CI = 0.73 to 0.96; P(trend) =.003); intake of tomato sauce, the primary source of bioavailable lycopene, was associated with an even greater reduction in prostate cancer risk (RR for 2+ servings/week versus <1 serving/month = 0.77; 95% CI = 0.66 to 0.90; P(trend)<.001), especially for extraprostatic cancers (RR = 0.65; 95% CI = 0.42 to 0.99). These associations persisted in analyses controlling for fruit and vegetable consumption and for olive oil use (a marker for Mediterranean diet) and were observed separately in men of Southern European or other Caucasian ancestry. Frequent consumption of tomato products is associated with a lower risk of prostate cancer. The magnitude of the association was moderate enough that it could be missed in a small study or one with substantial errors in measurement or based on a single dietary assessment.
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            Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression.

            L Fortlage, Steve Brown, John C Adair … (1997)
            The increase in oral availability of felodipine and other commonly used medications when taken with grapefruit juice has been assumed to be due to inhibition of CYP3A4, a cytochrome P450 that is present in liver and intestine. To evaluate the effect of repeated grapefruit juice ingestion on CYP3A4 expression, 10 healthy men were given 8 oz of grapefruit juice three times a day for 6 d. Before and after receiving grapefruit juice, small bowel and colon mucosal biopsies were obtained endoscopically, oral felodipine kinetics were determined, and liver CYP3A4 activity was measured with the [14C N-methyl] erythromycin breath test in each subject. Grapefruit juice did not alter liver CYP3A4 activity, colon levels of CYP3A5, or small bowel concentrations of P-glycoprotein, villin, CYP1A1, and CYP2D6. In contrast, the concentration of CYP3A4 in small bowel epithelia (enterocytes) fell 62% (P = 0.0006) with no corresponding change in CYP3A4 mRNA levels. In addition, enterocyte concentrations of CYP3A4 measured before grapefruit juice consumption correlated with the increase in Cmax when felodipine was taken with either the 1st or the 16th glass of grapefruit juice relative to water (r = 0. 67, P = 0.043, and r = 0.71, P = 0.022, respectively). We conclude that a mechanism for the effect of grapefruit juice on oral felodipine kinetics is its selective downregulation of CYP3A4 in the small intestine.
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              The role of tomato products and lycopene in the prevention of prostate cancer: a meta-analysis of observational studies.

              Bahi Takkouche, Francisco Caamaño-Isorna, Mahyar Etminan (2004)
              To determine whether intake of tomato products reduces the risk of prostate cancer using a meta-analysis. We systematically searched MEDLINE and EMBASE and contacted authors to identify potential studies. Log relative risks (RRs) were weighed by the inverse of their variances to obtain a pooled estimate with its 95% confidence interval (CI). Logistic regression and Poisson regression analyses were used to determine the effect produced by a daily intake of one serving of tomato product. Eleven case-control studies and 10 cohort studies or nested case-control studies presented data on the use of tomato, tomato products, or lycopene and met our inclusion criteria. Compared with nonfrequent users of tomato products (1st quartile of intake), the RR of prostate cancer among consumers of high amounts of raw tomato (5th quintile of intake) was 0.89 (95% CI 0.80-1.00). For high intake of cooked tomato products, this RR was 0.81 (95% CI 0.71-0.92). The RR of prostate cancer related to an intake of one serving/day of raw tomato (200 g) was 0.97 (95% CI 0.85-1.10) for the case-control studies and 0.78 (95% CI 0.66-0.92) for cohort studies. Our results show that tomato products may play a role in the prevention of prostate cancer. However, this effect is modest and restricted to high amounts of tomato intake. Further research is needed to determine the type and quantity of tomato products with respect to their role in preventing prostate cancer.
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                Author and article information

                Contributors
                Katsuyoshi Sunaga
                Journal
                Journal ID (nlm-ta): Asian J Pharm Sci
                Journal ID (iso-abbrev): Asian J Pharm Sci
                Title: Asian Journal of Pharmaceutical Sciences
                Publisher: Shenyang Pharmaceutical University
                ISSN (Print): 1818-0876
                ISSN (Electronic): 2221-285X
                Publication date PMC-release: 12 May 2017
                Publication date (Print): September 2017
                Publication date (Electronic): 12 May 2017
                Volume: 12
                Issue: 5
                Pages: 464-469
                Affiliations
                Laboratory of Pharmacotherapy, Department of Clinical Dietetics and Human Nutrition, Faculty of Pharmaceutical Sciences, Josai University, Keyakidai 1-1, Sakado, Saitama 350-0295, Japan
                Author notes
                [* ]Corresponding author. Faculty of Pharmaceutical Sciences, Josai University, Keyakidai 1-1, Sakado, Saitama 350-0295, Japan. Tel.: +81 49 2717269. ksunaga@ 123456josai.ac.jp
                [1]

                Present address: Development Division, Ryusendo Co., Ltd., Nishiikebukuro 1-5-3, Toshimaku, Tokyo, Japan.

                [2]

                Present address: Site Support Institute Co., Ltd., Minatoku, Shibaura 1-1-1, Tokyo, Japan.

                Article
                Publisher ID: S1818-0876(16)30187-8
                DOI: 10.1016/j.ajps.2017.05.004
                PMC ID: 7032185
                SO-VID: b526384b-eac2-4f8a-b723-5ef263239e5a
                Copyright © © 2017 Shenyang Pharmaceutical University. Production and hosting by Elsevier B.V.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 12 November 2016
                Date revision received : 29 April 2017
                Date accepted : 8 May 2017
                Categories
                Subject: Original Research Article

                Keywords: food–drug interactions,tomato juice,grapefruit juice,nifedipine,midazolam,pharmacokinetic interactions,tj, tomato juice,gfj, grapefruit juice,nfp, nifedipine,mdz, midazolam,auc, area under the concentration–time curve,cyp, cytochrome p450,9-oxo-oda, 9-oxo-10,12-octadecadienoic acid,13-oxo-oda, 13-oxo-9,11-octadecadenoic acid
                Data availability:
                Keywords: food–drug interactions, tomato juice, grapefruit juice, nifedipine, midazolam, pharmacokinetic interactions, tj, tomato juice, gfj, grapefruit juice, nfp, nifedipine, mdz, midazolam, auc, area under the concentration–time curve, cyp, cytochrome p450, 9-oxo-oda, 9-oxo-10,12-octadecadienoic acid, 13-oxo-oda, 13-oxo-9,11-octadecadenoic acid

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