Cranberry Juice Cocktail and Two Antibiotics
Cranberry Juice Cocktail and Two Antibiotics
Abstract & Commentary
By David Kiefer, MD. Dr. Kiefer is Clinical Instructor, Family Medicine, University of Washington, Seattle; Clinical Assistant Professor of Medicine, University of Arizona; and Adjunct Faculty, Bastyr University, Seattle; he reports no financial relationship to this field of study.
Synopsis: The oral absorption and clearance of either amoxicillin or cefaclor was tested in women who also ingested cranberry juice cocktail. Although there was modest slowing of absorption (amoxicillin and cefaclor) and decreased maximum serum drug concentration (cefaclor) when the cranberry groups were compared to control groups (water), the overall clinical effect seemed to be negligible.
Source: Li M, et al. Effects of cranberry juice on pharmacokinetics of b-lactam antibiotics following oral administration. Antimicrob Agents Chem 2009;53:2725-2732.
Cranberry juice (vaccinium macrocarpon) is a well-known botanical treatment and preventive for urinary tract infections (UTI) and, given that many patients combine dietary supplements with prescription medications often without the knowledge of their health care provider, there is the possibility for interactions between cranberries and antibiotics being used to treat or prevent UTI. This is the phenomenon that the researchers in this study attempted to explore.
The authors had identified in vitro data that led them to think that cranberry juice may affect the intestinal or renal drug transporters for amoxicillin and cefaclor, two antibiotics with different drug pharmacokinetics; amoxicillin kinetics involve both passive diffusion and active transport, whereas the more hydrophilic cefaclor involves a primarily active process.
In this trial, two groups of 18 women were assigned to receive either medication (two doses of amoxicillin, one dose of cefaclor) and cranberry juice or medication and water (see Table, page 127). Blood was drawn from an indwelling catheter at numerous time points and urine was collected at times 0, 2 hours, and 8 hours after medication administration to test for drug concentrations and to calculate pharmacokinetic parameters. Each of the four treatments was separated by a one-week washout period.
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The results of this study shed as much light on the pharmacokinetics of these antibiotics as on their interaction with cranberry juice. For example, serum levels and oral clearance were higher for the 2 g amoxicillin dose, as compared to the 500 mg dose, but the renal clearance was similar; the authors attributed this finding to the dose-dependent absorption of amoxicillin and probable saturation of the intestinal hPepT1 protein transporter. The maximum serum concentration (Cmax) and area under the concentration-time curve (AUC, or the total amount of drug in the blood after a dose) were similar for the water and cranberry juice groups, but the cranberry juice groups took longer (Tmax) to reach Cmax (P < 0.01), suggesting that cranberry juice did not affect the total amount of oral absorption but did slow the rate of oral absorption. There was no change in the elimination half-life, nor the renal clearance between the cranberry and control groups.
In contrast, the cefaclor group demonstrated a decrease in Cmax (P < 0.001) and an increase in Tmax (P < 0.05) for the cranberry vs. the water group, suggesting both a slower absorption rate and overall absorption in the presence of cranberry juice. As for the amoxicillin group, other parameters were similar between the cranberry and control groups.
The overall conclusion by the authors was that although there are some modest effects with the coadministration of cranberry juice cocktail and two antibiotics, it does not seem to be significant enough to have clinical relevance.
Commentary
The medical literature is rife with information about interactions between pharmaceuticals and dietary supplements. Many of these documented effects involve the cytochrome P450 system (CYP), the enzymes in the liver that process and detoxify myriad substances. As is now common knowledge, one of them, CYP3A4, processes approximately 50% of administered pharmaceuticals as well as many foods (grapefruit) and dietary supplements. Looking at interactions from a different angle, the idea that ingested substances may affect the absorption of medications is not new; we all recommend that fiber and calcium be taken separately from any pharmaceuticals so as not to adversely affect drug absorption. The authors of this study looked at possible absorption issues for two common antibiotics combined with a frequently used botanical, cranberry.
Looking at the research from the big picture, there are two reasons to doubt how clinically relevant or important the results are. Cranberry juice is used for both prevention and treatment of UTI, but while the first-line treatment of most UTI is occasionally amoxicillin, it is rarely cefaclor; there is, therefore, only a small chance that this study recreates a common clinical scenario. Although part of the interest of this study presumably was to look at two antibiotics with different pharmacokinetics, it nonetheless would have been more compelling to see results from UTI-relevant medications. Secondly, the women in this study were asked to take the antibiotic with water or cranberry juice; it could be argued that cranberry juice might be ingested during the day by someone suffering from or hoping to prevent a UTI, but not necessary at the time of antibiotic administration, two completely different scenarios for medication pharmacokinetics. It might have been structured more like real life to dose the cranberry juice throughout the day, and then check the parameters measured.
Furthermore, it is hard to dovetail this research with past investigations into the use of cranberry juice for UTI. A variety of cranberry formulations have been used in past research, from cranberry capsules, cranberry extracts, pure cranberry juice (a tough sell for regular consumption due to its strong flavor), cranberry-lingonberry (and sometimes other juices) combination, and cranberry juice of various percentages.1 This study used a cranberry juice cocktail (CJC), meant to approximate commonly sold (and purchased) products in the marketplace, as well as to match up with approved protocols as studied by the National Institutes of Health, as formulated by Ocean Spray. The fact that the product had industry connections is itself a concern, not to mention the fact that most CJC products have an alarming amount of sugar and/or high fructose corn syrup, likely to be more detrimental than helpful for overall health and wellness. This study would have been more convincing and interesting if it had tested pure cranberry juice, given that it is becoming more commonplace for health care providers to recommend the pure juice for UTI.
On the positive side, it is good to see an attempt to characterize the interactions that might exist between foods or dietary supplements and pharmaceuticals. With people increasingly turning to CAM modalities as first-line or adjunctive treatments for many common medical conditions, it will become more and more important to explore the details about possible interactions as they relate to metabolism or, as in the case of this study, absorption.
Reference
1. Jepson RG, Craig JC. Cranberries for preventing urinary tract infections. Cochrane Database Syst Rev 2008;(1):CD001321; doi: 10.1002/14651858. CD001321.pub4.
The oral absorption and clearance of either amoxicillin or cefaclor was tested in women who also ingested cranberry juice cocktail. Although there was modest slowing of absorption (amoxicillin and cefaclor) and decreased maximum serum drug concentration (cefaclor) when the cranberry groups were compared to control groups (water), the overall clinical effect seemed to be negligible.Subscribe Now for Access
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