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. Nordström, C. Halldin and L. Farde, Positron emission tomography studies on D2 dopamine receptor occupancy and plasma antipsychotic drug levels in man, Int. Clin. Psychopharmacol. 10 (Suppl. 3) (1995) 81-85. 14. P. J. Perry, Therapeutic drug monitoring of atypical antipsychotics. Is it of potential clinical value? CNS Drugs 13 (2000) 167-171. 15. M. C. Mauri, L. S. Volonteri, A. Colasanti, A. Fiorentini, I. F. de Gaspari and S. R. Bareggi, Clinical pharmacokinetics of atypical antipsychotics. A critical review of the relationship between plasma concentrations and clinical

-TNF biologic may be employed. However, in the context of optimal drug level with the presence of antidrug antibodies, the physician may stay on the current TNF inhibitor and monitor the drug level until there is lowering of clinical efficacy with low drug level and thereafter, may consider switching to another TNF inhibitor or to a non TNF biologic. 19 Therefore, checking the drug level and the presence of antidrug antibody level can guide one’s decision when one TNF inhibitor fails. There are limitations regarding the use of therapeutic drug monitoring and therefore, it is

, Shalviri G, Gholami K, Salamzadeh J, Maghooli G, Mirsaeedi SM. Adverse reactions of anti-tuberculosis drugs in hospitalized patients: incidence, severity and risk factors. Pharmacoepidemiol Drug Saf. 2007;16(10):1104-1110. 6. Peloquin CA. Therapeutic drug monitoring in the treatment of tuberculosis. Drugs. 2002;62(15):2169–83. 7. Mota L, Al-Efraij K, Campbell JR, Cook VJ, Marra F, Johnston J. Therapeutic drug monitoring in anti-tuberculosis treatment: a systematic review and meta-analysis. Int J Tuberc Lung Dis. 2016;20(6):819-826. 8. Weiner M, Burman W, Vernon A, et al

administration and one third of patients do not achieve total remission ( Cai et al., 2017 ). Therapeutic drug monitoring (TDM) is a beneficial patient management tool for quantification and subsequent interpretation of drug concentrations in blood in order to individualize and optimize pharmacotherapy. TDM enables individual dose adjustments according to the properties of the drug, patient characteristics, and measured concentration in blood. Therefore, it is considered as an important tool mainly in patients with variabilities in pharmacokinetics such as patients suffering

Abstract

A rapid, sensitive, high-throughput liquid chromatography coupled with tandem mass spectrometry method for the quantification of rivaroxaban from human plasma has been developed and validated. For the analytical separation a Zorbax SB-C18 column with isocratic flow of mobile phase composed of 0.2% formic acid in water and acetonitril (65:35, V/V) with a flow rate of 1 mL/min at a temperature of 45ºC was used. Detection of rivaroxaban was performed using positive electrospray ionization and MS/MS mode (sum of m/z 231.1; 289.2 and 318.2 from m/z 436.3). Plasma samples were prepared using single-step protein precipitation with methanol. Method validation was performed with regards to selectivity, linearity (r >0.9927), within-run and between-run precision (CV< 13.1 %) and accuracy (bias< 9.4 %) over a concentration range of 24.00 - 960.00 ng/mL plasma. Recovery was between 96.5 - 108.5% and the lower limit of quantification of rivaroxaban was 24.00 ng/mL. The developed method is simple, rapid, and selective, requires small plasma sample volumes, and was successfully applied for therapeutic drug monitoring of rivaroxaban in treated patients.

. Antiepileptic drugs - Best practice guidelines for therapeutic drug monitoring: A position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia . 2008;49:1239-1276. 6. Johannessen SI, Battino D, Berry DJ, et al. Therapeutic drug monitoring of the newer antiepileptic drugs. Ther Drug Monit . 2003;25:347-363. 7. Neels HM, Sierens AC, Naelaerts K, Scharpé SL, Hatfield GM, Lambert WE. Therapeutic drug monitoring of old and newer anti-epileptic drugs. Vol. 42, Clinical Chemistry and Laboratory Medicine; 2004. p. 1228

-Christie C, Guignard B, Zaugg C et al.: Impact of clinical Decision Support Guidelines on Therapeutic Drug Monitoring of Gentamicin in Newborns. Ther Drug Monit. 2014;36(5):656–662. [8] Barza M, Ioannidis JP, Cappelleri JC, Lau J et al.: Single and multiple daily doses of aminoglycosides a meta-analysis. BMJ. 1996;10(312):338–345. [9] Nezic L, Derungs A, Bruggisser M, Tschudin-Sutter S, Krähenbühl S, Haschke M: Therapeutic drug monitoring of once daily aminoglycoside dosing: comparison of two methods and investigation of the optimal blood sampling strategy. Eur J Clin

References BERTINO, J., S., Jr. - RODVOLD, K., A., DESTACHE, C., J.: Cost consideration in therapeutic drug monitoring of aminoglycosides. Clin Pharmacokinet, 26, 1, 1994, p. 71 - 81. ROBERTS, J., A. - PATERSON, D., L.- MARTIN, J., H.: Therapeutic drug monitoring of antimicrobials. Br J Clin Pharmacol, 73, 1, 2012, p. 27 - 36. CONNORS, J., E. - DIPIRO J., T. - SISLEY J., F.: Use of serum concentration in surgical patients. Am J Surg 156, 1, 1988, p. 68 - 76. MIGNAVAL, F. - FONTAINE, P., A. - RICHÉ, A. - NOWAK, C. - CANCEL, D. - LEMAITRE, F.: A Priori prediction

References 1. Venkataraman L, Burakoff SJ, Sen R. FK-506 inhibits antigen receptor-mediated induction of C-rel in B and T lymphoid cells. J Exp Med. 1995;181:1091-1099. 2. Plosker GL, Foster RH. Tacrolimus: a further update of its pharmacology and therapeutic use in the management of organ transplantation. Drugs. 2000;59:323-389. 3. Kang JS, Lee MH. Overview of therapeutic drug monitoring. The Korean Journal of Internal Medicine. 2009;24:1-10. 4. Wong G, Howard K, Chapman JR, Chadban S et al. Comparative survival and economic benefits of deceased donor kidney

Abstract

Augmented renal clearance (ARC) is a recently reported condition in pathophysiology of critically ill patients in the intensive care unit. ARC refers to the enhanced renal elimination of circulating solutes. These patients are either young or previously healthy people who have undergone surgery or multiple trauma.

This case report describes an adjustment of dosing regime of vancomycin to a young patient, who demonstrated ARC with severe polytrauma, overcome crush syndrome and sepsis. This 16-year old male patient was crushed by a tractor, which caused severe tissue damaged in the right lower limb. He gradually developed a serious crush syndrome. When kidneys resumed their function, creatinine clearance reached the value that indicated ARC (339.81 mL/min/1.73 m2). Vancomycin was included in the patient’s treatment regime by administering conventional dose of 1 g per 12 hours. The residual measured levels were very low. The dose of vancomycin had to be adjusted to double and then to triple the conventional dose. Without the therapeutic drug monitoring (TDM) and subsequent interpretation of the results by the clinical pharmacists, such high doses would not have been considered for administration.

ARC responds strongly to sub-therapeutic serum vancomycin levels. Our case report confirms the significance of TDM and the consecutive interpretation of the results in critically ill patients.