Clinical Pharmacokinetics Research Laboratory

Located in Lab Module 490 on Level 4 of Avedisian Hall

Overview

The Clinical Pharmacokinetics Research Laboratory is specialized in the areas of effect of disease states on drug disposition, pharmacokinetics and pharmacodynamics (PK/PD) modeling, and therapeutic drug monitoring (TDM). Located at the Kingston Campus of the University of Rhode Island, this laboratory is equipped with High Performance Liquid Chromatography (HPLC-UV, Hitachi) and ABI 3200 LC-Tandem Mass Spectrometry (LC-MS/MS, AB Sciex), a Xevo™ TQ MS (LC-MS/MS Waters), and a range of other instruments through RI-INBRE centralized core facility. We have established and validated different analytical methods for determination of immunosuppressive agents (i.e. cyclosporine, tacrolimus, sirolimus and mycophenolic acid) and other medications (listed below). In addition, we specialize in the measurement of free (unbound) drug concentration, either in plasma or oral fluids (saliva), and have established methods for determination of contrast media agents, iohexol or iodixanol, useful for accurate estimation of Glomerular Filtration Rate (GFR).

Concentration of total drug and metabolites in biological fluids for in vitro metabolism studies

  • Acetaminophen glucuronide, sulfate and glutathione metabolites (under development)
  • AZT (3′-azido-3′-deoxythymidine) glucuronidation as probe for UGT2B7 activity (LC-MS/MS)
  • Chlorzoxazone hydroxylation as probe for P450 2E1 activity (LC-MS/MS)
  • Cortisol metabolite (6 beta hydroxy cortisol) and free cortisol concentration in urine (under development)
  • Estradiol-glucuronidation as probe for UGT1A1 activity (HPLC-UV)
  • Midazolam, 1′-OH and 4-OH midazolam determination as probe for P450 3A4/5 activity (LC-MS/MS)

News

  • Professor named Ernest Mario Distinguished Chair in Pharmaceutics - Professor of Biomedical and Pharmaceutical Sciences Fatemeh Akhlaghi, who has gained a national reputation for her work on alcoholism, Type 2 diabetes, and measuring drug levels in organ transplant patients, has been named the Ernest Mario Distinguished Chair in Pharmaceutics. Professor Akhlaghi was named to the prestigious post this summer.
  • URI Professor Wins Grant to Study Possible Alcoholism Treatment - DR. FATEMEH AKHLAGHI, a University of Rhode Island professor of biomedical and pharmaceutical sciences, has received $1.65 million from the National Institutes of Health to study a new treatment for alcoholism in collaboration with Dr. Lorenzo Leggio of the National Institute on Alcohol Abuse and Alcoholism.
  • Diabetes patients on Lipitor needed for URI study - Plus you can earn an easy $40. KINGSTON, R.I. – September 10, 2010 – If you have diabetes and are taking Lipitor™ you might want to join a University of Rhode Island College of Pharmacy study that could help you and others with the disease. Fatemeh Akhlaghi, URI associate professor of biomedical and pharmaceutical sciences, […]
  • URI pharmacy researcher seeks participants - Lipitor metabolism study in patients with diabetes KINGSTON, R.I. – December 1, 2009 – A researcher in the University of Rhode Island’s College of Pharmacy is seeking subjects for a study focusing on the metabolism and side effects of Lipitor™ on patients with diabetes. Fatemeh Akhlaghi, URI associate professor of biomedical and pharmaceutical sciences, has […]
  • URI pharmacy professor has patent pending for pain-free method of monitoring drug levels in transplant patients - Use of saliva would reduce need for blood tests KINGSTON, R.I. – March 27, 2009 –The U.S. Patent and Trademark Office is reviewing a University of Rhode Island pharmacy professor’s proposal to use saliva as a non-invasive way to monitor concentrations of anti-rejection drugs in patients that undergo transplants. Associate Professor of Pharmacy Fatemeh Akhlaghi […]

Research

Current Projects

Biomarkers of T and B cell activity in immunosuppressed patients with diabetes mellitus

Pharmacokinetics and pharmacodynamics of prednisolone in diabetes

Pharmacokinetics of atorvastatin and metabolites

Pharmacokinetics of immunosuppressants in diabetic kidney transplant recipients

Salivary monitoring of immunosuppressive agents

Use of contrast media agents, iohexol and iodixanol, for determination of GFR

Effect of diabetes on the regulation of drug metabolizing enzymes

Publications

Please note that the copyright of the papers below rests with a variety of different parties. They are made available solely on the same basis that I would supply a single copy of a paper to an individual. It is up to you to ensure that your use of a paper does not infringe copyright law.

Current Medline Search for Dr. Akhlaghi’s Publications (PUBMED)

Published (in reverse chronological order)

60. Mohammadpour AH, Akhlaghi F. Future of Cholesteryl Ester Transfer Protein (CETP) Inhibitors: A Pharmacological Perspective. Clin Pharmacokinet. 2013 May 9. [Epub ahead of print]

59. Ogasawara K, Chitnis SD, Gohh RY, Christians U, Akhlaghi F. Multidrug resistance-associated protein 2 (MRP2/ABCC2) haplotypes significantly affect the pharmacokinetics of tacrolimus in kidney transplant recipients. Clin Pharmacokinet. 2013 Apr 30. [Epub ahead of print]

58, Dostalek M, Gohh RY, Akhlaghi F. Inosine monophosphate dehydrogenase expression and activity are significantly lower in kidney transplant recipients with diabetes mellitus. Ther Drug Monit. 35(3):374-83 (2013)

57. Chitnis SD, Ogasawara K, Schniedewind B, Gohh RY, Christians U, Akhlaghi F. Concentration of tacrolimus and major metabolites in kidney transplant recipients as a function of diabetes mellitus and cytochrome P450 3A gene polymorphism. Xenobiotica 2013 Jan 2. [Epub ahead of print]

56. Patel CG*, Ogasawara K*, Akhlaghi F. Mycophenolic acid glucuronide (MPAG) is transported by multidrug resistance-associated Protein 2 (MRP2) and this transport is not inhibited by cyclosporine, tacrolimus or sirolimus. Xenobiotica, 2012; Early Online: 1–7; * two authors contributed equally

55. Dostalek M*, Sam W-J*, Paryani KR, Macwan JS, Gohh RY, Akhlaghi F. Diabetes mellitus reduces the clearance of atorvastatin-lactone: the results of a population pharmacokinetic analysis in kidney transplant recipients and in vitro studies using human liver microsomes. Clin Pharmacokinet 51: 591-606 (2012) * two authors contributed equally.

54. Dostalek M, Akhlaghi F, Puzanovova M. Effect of diabetes mellitus on pharmacokinetic and pharmacodynamic properties of drugs. Clinical Pharmacokinetics; 51:481-99 (2012).

53. Longato L, Ripp K, Setshedi M, Dostalek M, Akhlaghi F, Branda M, Wands JR, de la Monte SM. Insulin resistance, ceramide accumulation, and endoplasmic reticulum stress in human chronic alcohol-related liver disease. Oxidative Medicine and Cellular Longevity 2012; 2012: 479348.

52. Macwan JS, Ionita IA, Akhlaghi F. A simple assay for simultaneous determination of rosuvastatin acid, rosuvastatin-5S-lactone, and N-desmethyl rosuvastatin in human plasma using liquid chromatography–tandem mass spectrometry (LC-MS/MS). Analytical and Bioanalytical Chemistry; 402: 1217–27 (2012).

51. Akhlaghi F, Dostalek F, Falck P, Mendonza AE, Amundsen R, Gohh RY, Åsberg A. The concentration of cyclosporine metabolites is significantly lower in kidney transplant recipients with diabetes mellitus. Ther Drug Monit; 34: 38-45 (2012).

50. Tsze DS, Steele DW, Machan JT, Akhlaghi F, Linakis JG. Intranasal ketamine for procedural sedation in pediatric laceration repair: a preliminary report. Pediatric Emergency Care 28: 767-70 (2012).

49. Elshafeey AH, Hamza YE, Amin SY, Akhlaghi F, and Zia H. Enhanced bioavailability of fenoterol transdermal systems in rabbits; Bioequivalence & Bioavailability, Volume 3: 097-100 (2011) – 097 (http://dx.doi.org/10.4172/jbb.1000067).

48. Dostalek M, Court MH, Yan B, Akhlaghi F. Significantly reduced cytochrome P450 3A4 expression and activity in liver from humans with diabetes mellitus. Br J Pharmacol; 163: 937-47 (2011).

47. Macwan JS, Ionita IA, Dostalek M, Akhlaghi F. Development and validation of a sensitive, simple, and rapid method for simultaneous quantitation of atorvastatin and its acid and lactone metabolites by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Anal Bioanal Chem. 400: 423-33 (2011)

46. Bolin P, Gohh R, Kandaswamy R, Shihab FS, Wiland A, Akhlaghi F, Melancon K. Mycophenolic acid in kidney transplant patients with diabetes mellitus: does the formulation matter? Transplantation Reviews 25: 117-23 (2011).

45. Dostalek M, Court MH, Hazarika S, Akhlaghi F. Diabetes mellitus reduce activity of human UDP-glucuronosyltransferase 2B7 (UGT 2B7) in liver and kidney leading to decreased formation of mycophenolic acid acyl-glucuronide metabolite. Drug Metab Dispos 39: 448-55 (2011)

44. Hu S, Akhlaghi F, Chitnis S, Chiu R, Go S, Rout P, Steffes M, Abbott JD, Dworkin L, Bostom A.  Comparison of plasma clearance of iodixanol during versus after angiography. Am J Kidney Dis. 56: 1219-20 (2010)

43. Narwal R, Akhlaghi F, Åsberg A, Hermann M, Rosenbaum SE. Development of a population pharmacokinetic model for atorvastatin acid and its lactone metabolite. Clin Pharmacokinet 49: 1-10 (2010).

42. Pabla D, Akhlaghi F, Zia H. Intestinal permeability enhancement of levothyroxine sodium by straight chain fatty acids studied in MDCK epithelial cell line. Eur J Pharm Sci. 40: 466-72 (2010).

41. Ionita IA, Akhlaghi F. Quantification of unbound prednisolone, prednisone, cortisol and cortisone in human plasma by ultrafiltration and direct injection into liquid chromatography tandem mass spectrometry. Ann Clin Biochem. 47:350-7 (2010).

40. Dostalek M, Macwan JS, Chitnis SD, Ionita IA, Akhlaghi F. Development and validation of a rapid and sensitive assay for simultaneous quantification of midazolam, 1′-hydroxymidazolam, and 4-hydroxymidazolam by liquid chromatography coupled to tandem mass-spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci.878:1629-33 (2010).

39. Akhlaghi F, Gohh RY. The level of ATP production in mitogen stimulated CD4+ lymphocytes is independent of the time of ingestion of immunosuppressive agents, Ther Drug Monitoring 32: 116-7 (2010).

38. Ionita IA, Fast DM, Akhlaghi F. Development of a sensitive and selective method for the quantitative analysis of cortisol, cortisone, prednisolone and prednisone in human plasma. J Chromatography B 877: 765-72 (2009).

37. Sam WJ, Akhlaghi F, Rosenbaum SE. Population pharmacokinetics of mycophenolic acid and its two glucuronidated metabolites in kidney transplant recipients. Journal of Clinical Pharmacology 49: 185-95 (2009).

36. Teasdale ME, Liu J, Wallace J, Akhlaghi F, Rowley DC. Secondary metabolites produced by a marine Halobacillus salinus that inhibit quorum sensing controlled phenotypes in Gram-negative bacteria. Applied Environmental Microbiology 75: 567-72 (2009).

35. Pabla D, Akhlaghi F, Zia H. A comparative pH-dissolution profile study of selected commercial levothyroxine products using inductively coupled plasma mass spectrometry. European Journal of Pharmaceutics and Biopharmaceutics 72: 105-10 (2009).

34. Mendonza AE, Gohh RY, Akhlaghi F. Blood and plasma pharmacokinetics of ciclosporin in diabetic kidney transplant recipients. Clinical Pharmacokinetics 47: 733-42 (2008).

33. Chitnis S, Akhlaghi F. Development and validation of HPLC-UV method for quantitative estimation of iodixanol in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci 869: 133-7 (2008).

32. Pabla D, Akhlaghi F, Ahmed A, Zia H. Development and validation of an inductively coupled plasma mass spectrometry method for quantification of levothyroxine in dissolution studies. Rapid Commun Mass Spectrom 22: 993-6 (2008).

31. Falck P, Åsberg A, Guldseth H, Bremer S, Akhlaghi F, Egge Reubsaet JL, Pfeffer P, Hartmann A, Midtvedt K. Declining intracellular T-lymphocyte concentration of cyclosporine a precedes acute rejection in kidney transplant recipients, Transplantation; 85: 179-84 (2008).

30. Patel CG, Richman K, Yang D, Yan B, Gohh RY, Akhlaghi F. Effect of diabetes mellitus on mycophenolate sodium pharmacokinetics and inosine monophosphate dehydrogenase activity in stable kidney transplant recipients; Therapeutic Drug Monitoring 29: 735-42 (2007).

29. Plante T, Harris D, Savitt J, Akhlaghi F, Monti J, Jay GD. Carboxyhemoglobin monitored by bedside continuous CO-oximetry. Journal of Trauma 63: 1187-90 (2007).

28. Mendonza AE, Zahir H, Gohh RY, Akhlaghi F. Tacrolimus in diabetic kidney transplant recipients: pharmacokinetics and application of a limited sampling strategy. Therapeutic Drug Monitoring 29: 391-98 (2007).

27. Shi D, Yang J, Yang D, Lecluyse EL, Black C, You L, Akhlaghi F, Yan B. Response to Comments on “anti-influenza prodrug oseltamivir is activated by carboxylesterase human carboxylesterase 1, and the activation is inhibited by antiplatelet agent clopidogrel’, Journal of Pharmacology and Experimental Therapeutics 322: 424-5 (2007).

26. Patel CG, Harmon M, Gohh RY, Akhlaghi F. Concentrations of mycophenolic acid and glucuronide metabolites under concomitant therapy with cyclosporine or tacrolimus. Therapeutic Drug Monitoring, 29: 87-95 (2007).

25. Shi D, Yang J, Yang D, Lecluyse EL, Black C, You L, Akhlaghi F, Yan B. Anti-influenza viral prodrug oseltamivir is activated by carboxylesterase HCE1 and the activation is inhibited by anti-platelet agent clopidogrel, Journal of Pharmacology and Experimental Therapeutics;319: 1477-84 (2006).

24. Zahir H, Keogh AM, Akhlaghi F. Apparent clearance of sirolimus in heart transplant recipients: impact of primary diagnosis and serum lipids, Therapeutic Drug Monitoring 28: 818-26 (2006).

23. Mendonza AE, Gohh RY, Akhlaghi F. Analysis of mycophenolic acid in saliva using liquid chromatography tandem mass spectrometry; Therapeutic Drug Monitoring 28: 402–6 (2006).

22. Akhlaghi F, Patel CG, Zuniga XP, Halilovic J, Preis IS, Gohh RY. Pharmacokinetics of mycophenolic acid and metabolites in diabetic kidney transplant recipients; Therapeutic Drug Monitoring 28: 95-101 (2006).

21. Rosenbaum SE, Akhlaghi F. Response to the Letter to the Editor by Dr Franck Saint-Marcoux et al. regarding a publication: Rosenbaum et al; Therapeutic Drug Monitoring 28: 139 (2006).

20. Patel CG, Akhlaghi F. High performance liquid chromatography method for the determination of mycophenolic acid and its acyl and phenol glucuronide metabolites in human plasma; Therapeutic Drug Monitoring 28: 116-22 (2006).

19. Akhlaghi F, Gonzalez ML, Trull AK. Association between cyclosporine concentrations at two hours post dose (C-2) and clinical outcomes in de novo lung transplant recipients; Journal of Heart Lung Transplantation 24: 2120-28 (2005).

18. Zahir H, McLachlan AJ, Nelson A, McCaughan G, Gleeson M, Akhlaghi F. Population pharmacokinetic estimation of tacrolimus apparent clearance in adult liver transplant recipients; Therapeutic Drug Monitoring 27: 422-30 (2005).

17. Rosenbaum SE, Baheti G, Trull AK, Akhlaghi F. Population pharmacokinetics of cyclosporine in cardiopulmonary transplant recipients; Therapeutic Drug Monitoring 27: 116-22 (2005).

16. Soman RS, Zahir H, Akhlaghi F. Development and validation of an HPLC-UV method for determination of iohexol in human plasma; J Chromatogr B Analyt Tchnol Biomed Life Sci. 25;816(1-2):339-43 (2005).

15. Patel CG, Mendonza AE, Akhlaghi F, Majid O, Trull AK, Lee T, Holt DW. Determination of total mycophenolic acid and its glucoronide metabolite using liquid chromatography with ultraviolet detection and unbound mycophenolic acid using tandem mass spectrometry; J Chromatogr B Analyt Technol Biomed Life Sci 813 :287-94 (2004).

14. Mendonza AE, Gohh R, Akhlaghi F. Determination of cyclosporine in saliva using liquid chromatography-tandem mass spectrometry; Therapeutic Drug Monitoring 26: 569-75 (2004).

13. Trull AK, Akhlaghi F, Charman SC, Endenberg S, Majid O, Cornelissen J, Steel L, Parameshwar J, Wallwork J, Large S. Immunosuppression, eotaxin and the diagnostic changes in eosinophils that precede early acute heart allograft rejection; Transplant Immunology 2: 159-66 (2004).

12. Ray J, Keogh AM, McLachlan AJ, Akhlaghi F, Cyclosporine C2 and C0 concentration monitoring in stable, long-term heart transplant recipients receiving metabolic inhibitors; Journal of Heart and Lung Transplantation 22: 715-22 (2003).

11. Akhlaghi F, Jackson C, Sharples L, Parameshwar J, Trull AK. Risk factors for the development and progression of dyslipidemia after heart transplantation; Transplantation 73:1258-64 (2002).

10. Akhlaghi F, Trull AK, Distribution of cyclosporin in organ transplant recipients, Clinical Pharmacokinetics 41(9): 615-37 (2002).

9. Akhlaghi F, Charman SC, Cornelissen J, Endenburg S, Majid O, Parameshwar J, Sharples LD, Steel LA,Trull AK, Wallwork J. Eotaxin and prednisolone concentrations regulate the mobilisation of peripheral blood eosinophils preceding heart allograft rejection; Journal of Heart and Lung Transplantation 20: 161 (2001).

8. Akhlaghi F, Holt DW, Lee T, Majid O, Trull AK. Simultaneous determination of plasma prednisolone, prednisone and cortisol by high performance liquid chromatography; Therapeutic Drug Monitoring 23: 163-68 (2001).

7. Akhlaghi F, Kaan A, Keogh AM, McLachlan AJ. Pharmacokinetics of cyclosporine in heart transplant recipients receiving metabolic inhibitors; Journal of Heart and Lung Transplantation 20: 431-38 (2001).

6. Trull AK, Steel LA, Sharples LD, Akhlaghi F, Parameshwar J, Cary N, Wallwork J, Large S. Randomized trial of blood eosinophil count monitoring as a guide to corticosteroid dosage adjustment after heart transplantation; Transplantation 5: 802-9 (2000).

5. Akhlaghi F, Ashley JJ, and Brown KF, Keogh AM. Variability in cyclosporine plasma unbound fraction in heart and lung transplant recipients; Therapeutic Drug Monitoring 21: 8-16 (1999).

4. Akhlaghi F, Brown KF, Keogh AM. Unbound cyclosporine and allograft rejection after heart transplantation; Transplantation 67: 54-9 (1999).

3. Akhlaghi F, Ashley JJ, Brown KF, Keogh AM. Indirect estimation of the fraction unbound of cyclosporine in plasma; Therapeutic Drug Monitoring 20: 301-8 (1998).

2. Akhlaghi F, Brown KF, Keogh A, McLachlan AJ. Effect of simvastatin on cyclosporine unbound fraction and apparent blood clearance in heart transplant recipients; British Journal of Clinical Pharmacology 44: 537-42 (1997).

1. Akhlaghi F. Distribution of cyclosporine in plasma from cardiopulmonary transplant recipients. PhD dissertation, Sydney: University of Sydney (1996).

 

Fatemeh Akhlaghi, Pharm.D., Ph.D.

Full Bio