Erythromycin Breath Test Publications

The authors used the ERMBT to show that, although omeprazole is a substrate for CYP3A4, the drug does not detectably influence in vivo CYP3A4 activity at therapeutic doses.

2. Harris, R.Z., S.M. Tsunoda, P. Mroczkowski, H. Wong, and L.Z. Benet. (1996) The effects of menopause and hormone replacement therapies on prednisolone and erythromycin pharmacokinetics. Clin. Pharmacol. Ther. 59:429-435.

The authors used the ERMBT to show that hormonally mediated differences in prednisolone kinetics do not appear to result from differences in CYP3A4 activity.

3. Stein, C.M., M.T. Kinirons, M. Pincus, G.R. Wilkinson, and A.J.J. Wood. (1996) Comparison of the dapsone recovery ratio and the erythromycin breath test as in vivo probes of CYP3A4 activity in patients with rheumatoid arthritis receiving cyclosporine. Clin. Pharmacol. Ther. 59:47-51.

The authors found a significant correlation between the ERMBT results and trough blood levels of cyclosporin A in patients with rheumatoid arthritis, confirming that liver CYP3A4 is largely rate limiting in the elimination of this drug.

4. Carbar, D., S. Dell’Orto, K. Morike, G.R. Wilkinson, D.M. Roden. (1997) Dietary salt increases first-pass elimination of oral quinidine. Cliin. Pharmacol. Ther. 61:292-300.

The authors report a highly significant correlation between the ERMBT and the in vivo rate of quinidine-3-hydroxylation in healthy volunteers, confirming in vitro derived data that quinidine 3-hydroxylation is catalyzed by CYP3A4 in vivo.

5. Cheng, C.L., D.E. Smith, P.L. Carver, S.R. Cox, P.B.Watkins, D.S. Blake, C.A. Kauffman, K. Meyer, G.L. Amidon, and P.L. Stetson. (1997) Steady state pharmacokinetics of delavirdine in HIV-positive patients: Effect on erythromycin breath test. Clin. Pharmacol. Ther. 51:531-543.

The authors use serial ERMBTs to show that delavirdine is a potent and reversible inhibitor of CYP3A4 activity in patients with AIDS. The investigators were able to estimate the plasma IC50 for delavirdine by correlating the plasma level with percent fall from baseline ERMBT result.

6. Lown, K.S., D.G. Bailey, R.J. Fontana, S.K. Janardan, C.H. Adair, L.A. Fortlage, M.B. Brown, W. Guo, and P.B. Watkins. (1997) Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression. J. Clin. Invest. 99:2545-2553.

The authors showed that in healthy volunteers the ERMBT results poorly predicted felodipine oral clearance when felodipine was taken with water. However, the correlation greatly improved when felodipine was taken with grapefruit juice, supporting the idea that the effect of grapefruit juice is to shift metabolism of felodipine from the intestine to the liver.

7. Gharaibeh, M.N., L.P. Gillen, B. Osborne, J.I. Schwartz, and S.A. Waldman. (1998) Effect of multiple doses of rifampin on the [14C N-methyl] erythromycin breath test in healthy male volunteers. J. Clin. Pharmacol. 38:492-495.

In this study, the reproducibility of the ERMBT was evaluated in eight male volunteers before and after oral administration of 600 mg of rifampin daily for 8 days. Two sequential ERMBT determinations performed 5 days apart before rifampin administration were highly reproducible. Rifampin induced CYP3A4 which was reflected in a 86 ± 30% (mean ± SD) increase in ERMBT values. Recovery of enzyme function after discontinuation of rifampin for 17 days was manifested as a return of ERMBT values to preinduction levels. These results support the utility of the ERMBT as a valid, reproducible, and reliable measure of CYP3A4 activity in vivo.

8. Tsunoda, S.M., Harris, R.Z., Mroczkowski, P.J., Benet, L.Z. (1998) Preliminary evaluatation of progestins as inducers of cytochrome P450 3A4 activity in postmenopausal women. J. Clin. Pharmacol. 38:1137-1143.

The effects of intramuscularly and orally administered medroxprogesterone acetate on cytochrome P450 3A4 (CYP3A4) activity were investigated in twelve postmenopausal women in a randomized, crossover study. Unbound prednisolone clearance and the erythromycin breath test were used as markers of CYP3A4 activity. After 2 months of intramuscular progestin therapy, unbound prednisolone clearance increased by 25% in five of six subjects. Similarly, after intramuscular progestin therapy, results from the erythromycin breath test showed a 23% mean increase in CYP3A4 activity. In contrast, 2 months of oral progestin therapy had no effect on prednisolone pharmacokinetics or erythromycin metabolism. These results suggest that parenterally but not orally administered progestins may induce or activate the CYP3A4 enzyme system, leading to an increased metabolism of many CYP3A4 substrates..

9. McCrea, J., B.J. Gertz, A. Carides, L. Gillen, S. Antonello, M.J. Brucker, C. Miller-Stein, B. Osborne, and S. Waldman. (1999) Concurrent administration of the erythromycin breath test (EBT) and oral midazolam as in vivo probes for CYP3A4 activity. J. Clin. Pharmacol. 39:1212-1220.

This study evaluated concomitant administration of intravenous [14C N-methyl] erythromycin and 2 mg oral midazolam as probes of systemic and of systemic plus presystemic CYP3A4 activity, respectively. Twelve males received the probes in a two-period crossover fashion; one period included the probes on two occasions, 5 days apart; in the second period, 200 mg ketoconazole was given orally 2 hours prior to the probes. The within-subject CV for ERMBT (% 14CO2/h) and midazolam (AUC) was 4.9% and 16.9%, respectively. Ketoconazole reduced the ERMBT by 43% and increased midazolam AUC by approximately fivefold. Concurrent administration of the ERMBT and oral midazolam was a sensitive and reproducible tool to screen new chemical entities for potentially important CYP3A4 interactions.

10. Polk, R.E., M.A. Crouch, D.S. Israel, A. Pastor, B.M. Sadler, G.E. Chittick, W.T. Symonds, W. Gouldin, and Y. Lou. (1999) Pharmacokinetic interaction between ketoconazole and amprenavir after single doses in healthy men. Pharmacotherapy 19:1378-1384.

The objective of this study was to determine the effects of coadministration of amprenavir and ketoconazole on the pharmacokinetics of both drugs and to assess the utility of the ERMBT to predict and explain these effects. The effects of the two drugs on the ERMBT are impressive. The effects of ketoconazole in this study was similar to that described by others, and it appears that under conditions of this study the potency of amprenavir's inhibition is similar to that of ketoconazole.

11. Hirth, J., P.B. Watkins, M. Strawderman, A. Schott, R. Bruno, and L.H. Baker. (2000) The effect of an individual's cytochrome CYP3A4 activity on docetaxel clearance. Clin. Cancer Res. 6(4):1255-8.

Docetaxel is a chemotherepeutic agent effective in the treatment of various solid tumors. Twenty-one patients with metastatic sarcomas received docetaxel (100 mg/m2). Hepatic CYP3A4 activity in each patient was measured by the ERMBT. Blood samples were taken at selected times over the next 24 h for pharmacokinetic analysis. The ERMBT was the best predictor of docetaxel clearance when compared with serum alanine aminotransferase, albumin, alkaline phosphatase, or serum alpha-1-acidic glycoprotein. The natural log of ERMBT accounted for 67% of the interpatient variation in docetaxel clearance. The greatest toxicity was seen in patients with the lowest ERMBT values. The data suggests that patients with low CYP3A4 activity (low ERMBT values) are at risk for having decreased docetaxel clearance and may thus experience increased toxicity from docetaxel. Those with high activity may be receiving a suboptimal dose. By measuring CYP3A4 activity, the ERMBT may be clinically useful in tailoring doses of CYP3A4 substrates, such as docetaxel, in certain individuals.

12. Prueksaritanont, T, Vega, J.M., Rogers, J.D., Galiano, K, Greenberg, H.E., Gillen, L., Brucker, M.J., McLoughlin, D., Wong, P.H., and Waldman, S.A. (2000) Simvastatin does not affect CYP3A activity, quantified by the erythromycin breath test and oral midazolam pharmacokinetics, in healthy male subjects. J. Clin. Pharmacol. 40(11):1274-9.

Potential for inhibition of CYP3A activity by simvastatin, an HMG-CoA reductase inhibitor, was evaluated in 12 healthy male subjects who received placebo or 80 mg of simvastatin, the maximal recommended dose, once daily for 7 consecutive days. On day 7, the ERMBT was co-administered with a 2 mg oral solution of midazolam. The values for the percent 14C exhaled during the first hour of the ERMBT and the pharmacokinetic parameters of midazolam (AUC, Cmax, t1/2) were not affected following multiple once-daily oral doses of simvastatin 80 mg. This data demonstrates that multiple dosing of simvastatin, at the highest recommended clinical dose, does not significantly alter the in vivo hepatic or intestinal CYP3A4/5 activity as measured by the commonly used ERMBT and oral midazolam probes.

13. Durr, Donat, Steiger, B., Kullak-Ublick, G.A., Rentsch, K.M., Steinert, H.C., Meier, P.J. and Fattinger, K. (2000) St. John’s Wort induces intestinal p-glycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin. Pharmacol. Ther. 68:598-604.

The administration of St John’s Wort to 8 healthy male volunteers during 14 days resulted in a 1.4-fold increase in the activity of CYP3A4 assessed by the erythromycin breath test. These results indicate the direct inducing effects of St John’s Wort on hepatic CYP3A4 in humans.

14. Polk, R.E., Brophy, D.F., Israel, D.S., Patron, R., Sadler, B.M., Chittick, G.E., Symonds, W.T., Lou, Y., Kristoff, D. and Stein, D.S. (2001) Pharmacokinetic interaction between amprenavir and rifabutin or rifampin in healthy males. Antimicrob. Agents Chemother. 45:502-8.

The objective of this study was to determine if there is a pharmacokinetic interaction when amprenavir is given with rifabutin or rifampin and to determine the effects of these drugs on the erythromycin breath test. Amprenavir inhibits the ERMBT by 83% and rifampin and rifabutin are equipotent inducers of the ERMBT, by 187% and 156%, respectively.

15. Schwartz, J.B. (2001) Race but not age affects erythromycin breath test results in older hypertensive men. J. Clin. Pharmacol. 41:324-9.

Erythromycin breath tests were performed to determine age and racial effects on CYP3A4-mediated hepatic clearance in hypertensive men (n=43). The data suggests that faster hepatic CYP3A4 activity in African American men compared to Caucasian men, and that race may significantly affect CYP3A4 hepatic clearance in patients treated for hypertension. Age, smoking and reported alcohol intake did not affect the ERMBT.

16. Haney, M.S., Hammes, R.J., Fine, F.P., Bianco, J.A. (2001) Effect of influenza immunization on CYP3A4. Vaccine 20:858-861.

Fifteen healthy subjects had erythromycin breath tests (ERMBT) before and after receiving influenza vaccine. The change in ERMBT following influenza immunization was not significant (mean -4%). Influenza immunization does not significantly change CYP3A4 activity.

17. Haas, C.E., Kaufman, D.C. and DiCenzo, R.C. (2001) Effects of metronidazole on hepatic CYP3A4 activity. Pharmacotherapy 21:1192-1195.

The objective of this study was to determine the effect of a short course of oral metronidazole, commonly used for bowel-preparation regimens, on hepatic CYP3A4 activity, as measured by the erythromycin breath test (ERMBT) in healthy volunteers. Subjects underwent a baseline ERMBT before receiving three oral doses of metronidazole (500 mg). Repeat ERMBTs were performed at 24, 72, and 96 hours after the initial ERMBT. The ERMBT values did not change significantly compared with baseline (p=0.82). The authors conclude that a short course of oral metronidazole does not result in a significant change in hepatic CYP3A4 activity.

18. Schmidt, L.E., Olsen, A.K., Stentoft, K., Rasmussen, A., Kirkegaard, P. and Dalhoff, K. (2001) Early postoperative erythromycin breath test correlates with hepatic cytochrome P4503A activity in liver transplant recipients. Clin. Pharmacol. Ther. 70(5):446-54.

The aim of this study was to investigate whether an early postoperative erythromycin breath test correlates with the hepatic CYP3A protein level and catalytic activity in liver transplant recipients. In 18 liver transplant recipients, the erythromycin breath test was performed within 2 hours after transplantation. A graft biopsy was obtained during surgery and analyzed for CYP3A protein level by Western blot technique, erythromycin demethylation and 6-beta-testosterone hydroxylation assays. The erythromycin breath test correlated with CYP3A protein level (r=0.60, p=0.01), erythromycin demethylation activity (r=0.76, p=0.0004) and 6-beta-testosterone activity (r=0.79, p=0.0001). The authors conclude that the erythromycin breath test is a specific in vivo assay of CYP3A activity in humans. The test is applicable in liver transplant recipients in the early postoperative phase.

19. Mouly, S., Lown, K.S., Kornhauser, D., Joseph, J.L., Fiske, W.D., Benedek, I.H., and Watkins, P.B. (2002) Hepatic but not intestinal CYP3A4 displays dose-dependent induction by efavirenz in humans. Clin Pharmacol Ther. 72:1-9.

The capacity of the non-nucleoside reverse transcriptase inhibitor efavirenz to induce either liver CYP3A4 or intestinal CYP3A4 or both, as well as intestinal P-glycoprotein, was evaluated in 12 healthy volunteers. Liver CYP3A4 activity was evaluated on 9 different occasions with use of the erythromycin breath test (ERMBT). Efavorenz significantly increased the mean ERMBT result in a dose- and time-dependent manner, with a 55% mean induction at 400 mg and a 33% mean induction at 200 mg. The efavirenz AUC on day 10 correlated with the magnitude of induction (r=0.509, p=0.04). In contrast, efavirenz treatment had no detectable effect on intestinal CYP3A4 or P-glycoprotein. These results suggest that drug interactions caused by induction of CYP3A4 can be liver specific.

20. Rivory, L.P., Slaviero, K.A., and Clark,e S.J. (2002) Hepatic cytochrome P450 3A drug metabolism is reduced in cancer patients who have an acute-phase response. Br J Cancer 87:277-80.

The purpose of this study was to assess cytochrome P450 3A function in patients with advanced cancer and its relation to the acute-phase response. Forty patients with advanced cancer were evaluated using the erythromycin breath test. Cancer patients with an acute phase response had reduced metabolism as measured with the erythromycin breath test. This indicates that the sub-group of cancer patients with significant acute-phase response have compromised drug metabolism, which may have implications for the safety of chemotherapy in this population.

21. Hayney, M.S. and Buck, J.M. (2002) Effect of age and degree of immune activation on cytochrome P450 3A4 activity after influenza immunization. Pharmacotherapy 22:1235-8.

The objective of this study was to measure age- or sex-related changes in cytochrome P450 (CYP3A4) activity secondary to influenza vaccination. Fifteen healthy volunteers aged 22-51 years old were given an erythromycin breath test (ERMBT) to measure CYP3A4 activity before influenza immunization and again on day 7 after immunization. Age of subject and change in ERMBT results after influenza immunization were correlated (r=-0.624, p<0.015). Decreases in CYP3A4 activity after influenza immunization are associated with increasing age.

22. Dowling, T.C., Brigli,a A.E., Fink, J.C., Hanes, D.S., Light, P.D., Stackiewicz, L., Karyekar, C.S., Eddington, N.D., Weir, M.R., and Henrich, W.L. (2003) Characterization of hepatic cytochrome P450 3A activity in patients with end-stage renal disease. Clin Pharmacol Ther. 73:427-34.

In experimental models of renal failure, both hepatic function and CYP enzyme content are reduced; however direct evidence in humans is lacking. Evaluation of drug metabolism in patients with end-stage renal disease is important because these patients use a large number of medications and are at risk of adverse reactions and drug-drug interactions. Hepatic CYP3A4 activity at baseline and after rifampin enzyme induction in 12 patients with end-stage renal disease and 12 healthy, age-matched controls was evaluated. Hepatic CYP3A4 phenotype was characterized with the erythromycin breath test and enzyme induction capacity was evaluated with a short course of rifampin (600 mg/d for 6 days). The end-stage renal disease group had 28% lower baseline erythromycin breath test values than controls (p<0.05); however, enzyme induction capacity after rifampin administration was similar between groups. The findings suggested that one mechanism by which patients with end-stage renal disease are at increased risk of drug toxicity is reduced activity of the CYP3A4 enzyme pathway.

23. Haas, C.E., Kaufman, D.C., Jones, C.E., Burstein, A.H., and Reiss, W. (2003) Cytochrome P450 3A4 activity after surgical stress. Crit Care Med 31:1338-46.

The objective of this study was to evaluate the relationship between the acute inflammatory response after surgical trauma and changes in hepatic cytochrome P450 3A4 activity, compare changes in CYP 3A4 activity after procedures with varying degrees of surgical stress and to explore the time course of any potential drug-cytokine interaction after surgery. A total of 16 patients scheduled for elective surgery had CYP 3A4 activity estimated by the erythromycin breath test (ERMBT) before and after surgery (6, 24, 32, 48 and 72 hours after surgery). ERMBT results significantly declined after surgery with the lowest value at 72 hours. Acute inflammation after elective surgery was associated with a significant decline in CYP3A4 activity which is predictive of clinically important changes in the metabolism of commonly used drugs that are substrates for this enzyme.

24. Salvat, C., Mouly, S., Rizzo-Padoin, N., Knellwol,f A.L., Simoneau, G., Duet, M., Nataf, V., Bailliart, O., and Bergmann, J.F. (2003) The [14C-N-methy]-erythromycin breath test dosimetry complies with the French regulations for radiation safety. Fundam Clin Pharmacol. 17:349-53.

In order to extend the use of this test in France safety data was obtained from patient dosimetry and worker exposure to [14C-N-methyl]-erythromycin. The radioactivity administered to a patient after one 14C-ERMBT was equal to 108.9 kBq leading to a patient effective dose of 20 microsievert (microSv) and a maximum effective dose after14CO2 inhalation by the exposed worker of 16 microSv compared with a mean individual annual effective dose from natural and artificial radioactivity exposure of 3500 microSv in France. “The 14C-ERMBT is safe and complies with the European regulations regarding the administration of 14C-labeled compounds in humans. It can therefore be used in clinical research in France without any particular safety requirement.”

25. Schmidt, L.E., Rasmussen, A., Kirkegaard, P., and Dalhoff, K. (2003) Relationship between postoperative erythromycin breath test and early morbidity in liver transplant recipients. Transplantation 76:358-63.

Early postoperative erythromycin breath test (ERMBT) is an in vivo measure of graft CYP3A4 activity. This study evaluates the usefulness of an early postoperative ERMBT in predicting early morbidity in liver transplant recipients. In 26 liver transplant recipients, ERMBT was performed within 2 hr after transplantation. Main end points were the occurrence of cyclosporine and tacrolimus nephrotoxicity, episodes of early graft rejection, early graft function and graft survival. Cyclosporine and tacrolimus nephrotoxicity were associated with low postoperative ERMBT values. There was a significant inverse correlation between postoperative ERMBT values and the time to normalization of international normalized ratio as a measure of early graft function. An early postoperative ERMBT may be useful in predicting the development of cyclosporine and tacrolimus nephrotoxicity, severe graft dysfunction or even graft loss in liver transplant recipients when calcineurin inhibitors are administered according to protocols.

26. Lemahieu, W.P, Maes, B.D., Ghoos, Y., Rutgeerts, P., Verbeke, K., and Vanrenterghem, Y. (2003) Measurement of hepatic and intestinal CYP3A4 and PGP activity by combined po + iv [14C]erythromycin breath and urine test. Am J Physiol Gastrointest Liver Physiol. 285:G470-82.

The aim of this study was to develop a test for measuring hepatic and intestinal removal of CYP3A4 and P-glycoprotein (PGP)-dependent xenobiotics that would be applicable for clinical use in humans. Orally and intravenously administered [N-methyl-14C]erythromycin was used for evaluation of 14C-labeled excretion dynamics in breath and urine. Simultaneous breath and urine test measurements were performed in 3 healthy volunteers and in 23 renal transplant recipients. Mathematical analysis permitted separation of both CYP3A4 and PGP activity in the liver and intestine. It is concluded that the combined oral and intravenous erythromycin breath and urine test is a reliable and noninvasive test to measure phenotypic intestinal and hepatic CYP3A4 and PGP activity.

27. Veronese, M.L., Gillen, L.P., Burke, J.P., Dorval, E.P., Hauck, W.W., Pequignot, I., Waldman, S.A., and Greenberg, H.E. (2003) Exposure-dependent inhibition of intestinal and hepatic CYP3A in vivo by grapefruit juice. J Clin Pharmacol. 43:831-9.

The current study compared the effects of consuming large quantities and more typical amounts of grapefruit juice (GFJ) on the activity of hepatic and intestinal CYP3A4 by employing the erythromycin breath test (ERMBT) and oral midazolam pharmacokinetics. The data suggests that GFJ inhibits intestinal and hepatic CYP3A4 in an exposure-dependent fashion and that patients taking medications that are CYP3A4 substrates are at risk for developing drug-related adverse events if they consume large amounts of grapefruit juice.

28. Veronese, M.L., Gillen, L.P., Dorval, E.P., Hauck, W.W., Waldman, S.A., and Greenberg, H.E. (2003) Effect of mibefradil on CYP3A4 in vivo. J Clin Pharmacol 43:1091-1100.

Mibefradil, a calcium channel blocker, was removed from the market because of adverse drug interactions with coadministered CYP3A4 substrates. This study examined the effect of mibefradil on the activity of hepatic and intestinal CYP3A4 in vivo, employing the erythromycin breath test (ERMBT) and oral midazolam pharmacokinetics. The data support that adverse drug interactions involving mibefradil reflects inhibition of CYP3A4 in intestine and liver.

29. Hayney, M.S. and Muller, D. (2003) Effect of influenza immunization on CYP3A4 activity in vivo. J. Clin Pharmacol. 43:1377-81.

The authors hypothesized that changes in CYP3A4 activity following influenza immunization would correlate with cytokine production or age. Twenty-four subjects had an erythromycin breath test (ERMBT) and blood draw for lymphocyte culture prior to and on day 7 following influenza immunization. The interferon gamma production correlated with the change in ERMBT. This correlation supports in vitro findings of decreased CYP3A4 expression and activity with interferon gamma exposure.

30. Slaviero, K,A,, Clarke, S.J., McLachlan, A.J., Blair, E.Y. and Rivory, L.P. (2004) Population pharmacokinetics of weekly docetaxel in patients with advanced cancer. Br J Clin Pharmacol. 57:44-53.

The aims of this study were to investigate the pharmacokinetics of docetaxel in patients with advanced cancer and to utilize a population pharmacokinetic approach to predict docetaxel clearance. A population pharmacokinetic model was developed and validated for weekly docetaxel in patients with advanced cancer. These results indicated that CYP3A4 activity and hepatic function have an impact on the pharmacokinetics of docetaxel when administered weekly.

31. Lau, W.C., Gurbe,l P.A., Watkins, P.B., Nee,r C.J., Hopp, A.S., Carville, D.G., Guyer, K.E., Tait, A.R. and Bates, E.R. (2004) Contribution of hepatic cytochrome P450 3A4 metabolic activity to the phenomenon of clopidogrel resistance. Circulation 109:166-71.

Interindividual variability of platelet inhibition after aspirin or clopidogrel administration has been described. Because the prodrug clopidogrel is activated by hepatic CYP3A4, it was hypothesized that interindividual variability in clopidogrel efficacy might be related to interindividual differences in CYP3A4 metabolic activity. Platelet aggregation was measured before and after clopidogrel treatment in 32 patients undergoing coronary artery stent implantation and in 35 healthy volunteers. The erythromycin breath test was used to measure CYP3A4 activity. Percent platelet aggregation after clopidogrel inversely correlated with CYP3A4 activity (r=-0.5, p=0.003). Clopidogrel administration results in interindividual variability in platelet inhibition, which correlates with CYP3A4 metabolic activity.

32. DeVane, C.L., Donovan, J.L., Liston, H.L., Markowitz, J.S., Cheng, K.T., Risch, S.C. and Willard, L. (2004) Comparative CYP3A4 inhibitory effects of venlafaxine, fluoxetine, sertraline, and nefazodone in healthy volunteers. J Clin Psychopharmacol. 24:4-10.

An antidepressant for use in the patient receiving concomitant drug treatment, over-the-counter medications, or herbal products should lack CYP3A4 inductive or inhibitory activity to provide the least likelihood of a drug-drug interaction. This study addresses the potential of 4 diverse antidepressants (venlafaxine, nefazodone, sertraline, and fluoxetine) to inhibit or induce CYP3A4. CYP3A4 activity was evaluated for each subject at baseline and following each antidepressant using the eythromycin breath test. Compared to baseline, venlafaxine, sertraline, and fluoxetine caused no apparent inhibition or induction in CYP3A4 levels. Nefaxodone was the only antidepressant that caused a significant inhibition in CYP3A4 levels. These results demonstrate different effects amongst antidepressants for altering CYP3A4 activity.

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