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Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Determination of Azole Antifugals in Human Serum
Posters Methods: Simple sample preparation using protein precipitation by mixture of acetonitrile-methanol (40:60, v/v) with zinc sulfate and fast gradient liquid chromatography-tandem mass spectrometry provided an effective method for the use in routine clinical settings. The separation was performed on a BEH C18 column (2.1 x 50 mm, 1.7µm) by using binary mobile phase (A: 0.1% formic acid in water, v/v; B: 0.1% formic acid in acetonitrile, v/v). Alprenolol was applied as an internal standard. Mass spectrometric detection was carried out in the positive electrospray ionization mode. Results: The method was validated over the concentration range of 0.13–100 ng/mL with overall recovery of haloperidol 96.7 % - 100.0 %. The intra-day and inter-day precisions determined at the three concentration levels were in the range of 1.4 % to 9.7 %. Selected reaction monitoring and negligible matrix effect allow to achieve a required quantification limit. Conclusions: The presented method is applicable to routine therapeutic drug monitoring of haloperidol in clinical practice with a reasonable short analysis time (5 min).
Quantitative Analysis of Fluphenazine and Flupentixol in Human Serum by Liquid Chromatography-Tandem Mass Spectrometry P. Sistik1,2,3; R. Urinovska1,3; H. Brozmanova1,3; I. Kacirova1,3; and K. Lemr2 1 University Hospital Ostrava, Ostrava, Czech Republic; 2Palacky University Olomouc, Olomouc, Czech Republic; and 3University of Ostrava, Ostrava, Czech Republic Background: The optimal use of therapeutic drug monitoring (TDM) in psychiatry is discussed in the guidelines of the TDM expert group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie. Regarding fluphenazine and flupentixol, the TDM is “strongly recommended” and “recommended”, respectively. An accurate, sensitive, reproducible, and selective liquid chromatography/tandem mass spectrometry (LC–MS/MS) method for their quantitation in human plasma was developed and validated. Methods: 200 µL human serum was cleaned up using a protein precipitation by acetonitrile-methanol (40:60, v/v) with zinc sulfate. Alprenolol was applied as an internal standard (IS) as the substance is currently not used in human medicine by the European Medicines Agency. Liquid chromatography was performed using a short BEH C18 column (2.1 x 50 mm, 1.7µm) and binary mobile phase gradient (A: 2 mmol/L ammonium acetate, 0.1% formic acid in 5% acetonitrile, v/v/v; B: 2 mmol/L ammonium acetate, 0.1% formic acid in 95% acetonitrile, v/v/v) to achieve short analysis time. Results: The method was validated in the concentration range of 0.16–100 ng/mL. Detection was performed in positive electrospray ionization and selected reaction monitoring mode (2 ion transitions per a compound). Limits of quantitation were below a therapeutic reference range. For both analytes, the intra-run and inter-run precision were between 2.6 % - 11.3 % and 7.6 % - 12.2 %, respectively, the overall recovery was between 87.2 % and 101.1 %. Conclusions: The developed method was introduced into routine clinical practice and suitably has broadened the spectrum of antipsychotics monitored in our hospital.
Development of Liquid Chromatography Method Coupled With Mass Spectrometry for Analysis of the Vitamins in Human Serum R. Urinovska1,2; and P. Sistik1,2 University Hospital Ostrava, Ostrava, Czech Republic; and 2 University of Ostrava, Ostrava, Czech Republic
1
August 2017
Background: Vitamins are organic substances with different chemical structure, divided into water-soluble vitamins (hydrophilic) and fat-soluble (lipophilic). They are low molecular weight compound required for a number of biochemical functions. The aim of this study was developed a new method for determination of vitamin A (retinol), E (alpha-tocopherol), C (ascorbic acid), B1 (thiamine), B2 (riboflavin), B6 (pyridoxal), and folic acid in the serum by liquid chromatography coupled with mass spectrometry (UPLC-MS/MS). Methods: Analysis was performed on a Waters UPLC H-class system (Waters, Milford MA, USA) coupled with triple quadrupole XEVO TQD (Micromass, Manchester, UK). The separation of vitamins was carried on BEH C18 column, using mobile phase gradient (water: acetonitrile: formic acid), time of analysis was 13 min. Serum was directly analysed after protein precipitation using an organic solvent. Results: The method showed a good linearity in the range of 2.5 - 500 nmol/L for folic acid and vitamin B1; 2.5 - 1500 nmol/L for vitamins B2 and B6; 1-500 µmol/L for vitamin C; 25 - 5000 nmol/L for vitamin A and 0.5 - 250 µmol/L for vitamin E. The limits of quantification were for all substances under therapeutic reference range. Conclusions: An analytical method using protein precipitation and liquid chromatography/tandem mass spectrometry was developed and optimized for the quantification of seven vitamins in human serum and was successfully applied in routine practice. Method validation was performed according to the FDA rules.
Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Determination of Azole Antifugals in Human Serum H. Brozmanova1,2; R. Urinovska1,2; P. Sistik1,2; I. Kacirova1,2; and M. Grundmann1 1 University of Ostrava, Ostrava, Czech Republic; and 2University Hospital Ostrava, Ostrava, Czech Republic Background: Azole antifugals are used for the prevention and in the treatment of invasive life threatening fungal infections. The most commonly administrated antifugal agents are the triazole compounds fluconazole, voriconazole, posaconazole and intraconazole. Therapeutic monitoring of the triazoles is recommended to assure sufficient and safe concentrations in serum Methods: A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of fluconazole (FLU), ketoconazole (KET), voriconazole (VOR), posaconazole (POS), itraconazole (ITR) and its active metabolite hydroxy- itraconazole (OH-ITR) was developed. 100 µL of 0.5 mol/L formic acid and 0.5 mL of acetonitrile with zinc sulphate were added to 200 µL of human serum. The mixture was vortex mixed and centrifuged in cold for 10 minutes. Supernatant was used for analysis. Chromatographic conditions were as follows: Column BEH C18 50x2.1, 1.7µm, mobile phase composed from water, acetonitrile, 2 mmol/L ammonium acetate and a 0.1% formic acid. Rate of mobile phase was 0.4 mL /min, temperature of column was maintained at 50 oC and time of analysis was 5 minutes. Ascomycin D was used as an internal standard. Results: Calibration curves were used in the range of 0.1-100 mg/L for FLU and 0.01-10 mg/L for KET, VOR, POS, ITR and its metabolite OH-ITR. Coefficient of variations (intraassay and interassay) was found between 1.7-10.1 % and recovery from 86.3 to 111.1 %. Conclusions: New LC-MS/MS method for analysis of azole antifugals concentrations was developed and validated. This method is fast and precise with simple sample extraction and has been introduced into routine therapeutic drug monitoring.
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Clinical Therapeutics Liquid Chromatography-Tandem Mass Spectrometry Method for Determination of Gentamicin Concentrations and Comparison with Two Immunoassay Methods (Chemiluminiscent Assay a Polarization Fluoroimmunoassay) H. Brozmanova1,2; R. Urinovska2; P. Sištik2; I. Kacirova1,2; and M. Grundmann1 1 University of Ostrava, Ostrava, Czech Republic; and 2University Hospital Ostrava, Ostrava, Czech Republic Background: Gentamicin belongs to aminoglycoside antibiotics. Therapeutic drug monitoring (TDM) of gentamicin is recommended for all patients to assure both sufficient and safe concentrations in blood. Gentamicin is composed from a mixture of three drugs (C1, C1A and C2A +C2) with the basic share as follows: C1 25-50%, C1A 10-35% and C2A + C2 25-55%. Gentamicin concentrations are preferably measured using immunoanalytical assays. Methods: A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with simple sample extraction and a relatively short time of gentamicin analysis was developed and validated. 50 µL of serum was precipitated using acetonitrile and formic acid. A RP BEH C18, 1.7 µm, 2.1 x 50 mm column maintained at 30oC and tobramycin as internal standard were used. Mass detection was performed in positive electrospray mode. The results were compared with analyses of polarization fluoroimmunoassay (FPIA) method (Abbott AxSYM) and a chemiluminiscent assay (Advia Centauer, Siemens). Passing-Bablok regression analysis and Bland-Altman analysis were used to compare gentamicin concentrations. Results: Calibration curve was linear in the range of 0.1-50 mg/L. Recovery was 91.6-102.0% with a coefficient of variations of 1.4-8.4% for single types of gentamicin. The sum of gentamicin concentrations correlated significantly with both immunoanylatical assays. Conclusions: Presented LC-MS/MS method is fast and precise with simple sample extraction and can be applied for routine TDM of gentamicin.
Liquid Chromatography-Tandem Mass Spectrometry Method for Tdm of Vancomycin and Comparison with Results of Polarization Fluoroimmunoassay H. Brozmanova1,2; I. Kacirova1,2; R. Urinovska1,2; P. Sistik1,2; and M. Grundmann1 1 Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic; and 2University Hospital Ostrava, Ostrava, Czech Republic Background: Vancomycin is a glycopeptide antibiotic with a strong bactericidal activity used for the treatment of serious infections caused by gram-positive bacteria including methicillin-resistant Staphylococcus aureus. Therapeutic drug monitoring (TDM) of vancomycin is highly valuable due to the large interpatient and intra patient variability of pharmacokinetics. Methods: A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with simple sample extraction and a relatively short time of vancomycin analysis was developed and validated. 50 µL of serum was precipitated using 33% trichloroacetic acid, and NH4OH was added to increase pH before analysis. A RP BEH C18, 1.7 µm, 2.1 x 50 mm column maintained at 30oC and tobramycin as internal standard were used. Mass detection was performed in positive electrospray mode. The results were compared with analyses of polarization fluoroimmunoassay (FPIA) method (Abbott AxSYM). Subjects were divided into three groups according to serum creatinine levels (normal 53.5±19.1, 150.2±48.4 and 471.7±124.7 in dialyzed
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patients). Passing-Bablok regression analysis and Bland-Altman analysis were used to compare vancomycin concentrations. Results: Calibration curve was linear in the range of 0.1-100 mg/L. Recovery was 98.2-104.9% with a coefficient of variations of 1.77.2%. Vancomycin concentrations from dialyzed patients with the highest serum creatinine levels were about 14% greater than results from the FPIA assay. Conclusions: Presented LC-MS/MS method is fast and precise with simple sample extraction. These analytical conditions enable to receive the vancomycin concentrations early and along with interpretation of clinical pharmacologist make the dosage adjustment before the administration of the next vancomycin dose.
Improved Clinical Outcomes in paediatric Epileptic Patients on Lamotrigine therapy after implementation of Therapeutic drug monitoring B. Koristkova1,2; M. Grundmann1; I. Kacirova1,2; and H. Brozmanova1,2 1 University of Ostrava, Ostrava, Czech Republic; and 2University Hospital Ostrava, Ostrava, Czech Republic Background: Therapeutic drug monitoring (TDM) of lamotrigine has been recommended. Lamotrigine elimination by UGT is sensitive to induction and inhibition. Concomitant therapy with both enzyme inducers and inhibitors was described to be fully or partially compensated. The aim of our study was to analyse the impact of TDM on clinical outcomes of patients and importance of possible drug interactions, especially in triple combinations of antiepileptic drugs. Methods: During the period of 2001-2015 1308 pre-dose samples were taken from 430 patients < 15 years old as part of routine TDM. Drug interactions were evaluated using calculation of lamotrigine clearance. Mann-Whitney U-test for median values; χ 2-test for incidence of seizures, adverse drug reactions (ADRs) and distribution of plasma levels according to therapeutic range (TR) of 3-14 mg/L were calculated with aid of Prism 5.0, GraphPad Software. Results: Only 61% of samples reached TR during 2001-2005, compared to 74-75% during 2006-2015. TR was exceeded in 2% of cases in monotherapy, and in 6-7% of cases in combination therapy. ADRs were reported in 22 of cases (2%), more frequently in bi- and triple therapy. Seizures occurred more often daily and monthly during the first period, in patients with levels below TR, and in two or three antiepileptic drugs in combination. Carbamazepine and topiramate in bitherapies increased clearance of lamotrigine by 200% and 24%. Valproic acid decreased lamotrigine clearance by 53% in bitherapy, by 50% and 56% in triple therapy with levetiracetam and topiramate but only by 21% in triple therapy with carbamazepine. Levetiracetam had no effect on lamotrigine clearance. Conclusions: Long-term provided TDM led to decreased of seizure frequency in paediatric epileptic patients on lamotrigine therapy. The inhibitive effect of valproate was only partially decreased by carbamazepine.
Drug Interaction Between Clarithromycin And Tacrolimus – A Case Report B. Koristkova1,2; M. Grundmann1; I. Kacirova1,2; and R. Urinovska1,2 1 University of Ostrava, Ostrava, Czech Republic; and 2University Hospital Ostrava, Ostrava, Czech Republic A 16-year-old man (66 kg, 175 cm) after preemptive kidney transplantation from living donor (mother) in June 2017, was treated with tacrolimus (Prograf®) 1.5 mg twice daily (b.i.d.) and mycophenolate
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Quantitative Analysis of Fluphenazine and Flupentixol in Human Serum by Liquid Chromatography-Tandem Mass Spectrometry P. Sistik1,2,3; R. Urinovska1,3; H. Brozmanova1,3; I. Kacirova1,3; and K. Lemr2 1 University Hospital Ostrava, Ostrava, Czech Republic; 2Palacky University Olomouc, Olomouc, Czech Republic; and 3University of Ostrava, Ostrava, Czech Republic Background: The optimal use of therapeutic drug monitoring (TDM) in psychiatry is discussed in the guidelines of the TDM expert group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie. Regarding fluphenazine and flupentixol, the TDM is “strongly recommended” and “recommended”, respectively. An accurate, sensitive, reproducible, and selective liquid chromatography/tandem mass spectrometry (LC–MS/MS) method for their quantitation in human plasma was developed and validated. Methods: 200 µL human serum was cleaned up using a protein precipitation by acetonitrile-methanol (40:60, v/v) with zinc sulfate. Alprenolol was applied as an internal standard (IS) as the substance is currently not used in human medicine by the European Medicines Agency. Liquid chromatography was performed using a short BEH C18 column (2.1 x 50 mm, 1.7µm) and binary mobile phase gradient (A: 2 mmol/L ammonium acetate, 0.1% formic acid in 5% acetonitrile, v/v/v; B: 2 mmol/L ammonium acetate, 0.1% formic acid in 95% acetonitrile, v/v/v) to achieve short analysis time. Results: The method was validated in the concentration range of 0.16–100 ng/mL. Detection was performed in positive electrospray ionization and selected reaction monitoring mode (2 ion transitions per a compound). Limits of quantitation were below a therapeutic reference range. For both analytes, the intra-run and inter-run precision were between 2.6 % - 11.3 % and 7.6 % - 12.2 %, respectively, the overall recovery was between 87.2 % and 101.1 %. Conclusions: The developed method was introduced into routine clinical practice and suitably has broadened the spectrum of antipsychotics monitored in our hospital.
Development of Liquid Chromatography Method Coupled With Mass Spectrometry for Analysis of the Vitamins in Human Serum R. Urinovska1,2; and P. Sistik1,2 University Hospital Ostrava, Ostrava, Czech Republic; and 2 University of Ostrava, Ostrava, Czech Republic
1
August 2017
Background: Vitamins are organic substances with different chemical structure, divided into water-soluble vitamins (hydrophilic) and fat-soluble (lipophilic). They are low molecular weight compound required for a number of biochemical functions. The aim of this study was developed a new method for determination of vitamin A (retinol), E (alpha-tocopherol), C (ascorbic acid), B1 (thiamine), B2 (riboflavin), B6 (pyridoxal), and folic acid in the serum by liquid chromatography coupled with mass spectrometry (UPLC-MS/MS). Methods: Analysis was performed on a Waters UPLC H-class system (Waters, Milford MA, USA) coupled with triple quadrupole XEVO TQD (Micromass, Manchester, UK). The separation of vitamins was carried on BEH C18 column, using mobile phase gradient (water: acetonitrile: formic acid), time of analysis was 13 min. Serum was directly analysed after protein precipitation using an organic solvent. Results: The method showed a good linearity in the range of 2.5 - 500 nmol/L for folic acid and vitamin B1; 2.5 - 1500 nmol/L for vitamins B2 and B6; 1-500 µmol/L for vitamin C; 25 - 5000 nmol/L for vitamin A and 0.5 - 250 µmol/L for vitamin E. The limits of quantification were for all substances under therapeutic reference range. Conclusions: An analytical method using protein precipitation and liquid chromatography/tandem mass spectrometry was developed and optimized for the quantification of seven vitamins in human serum and was successfully applied in routine practice. Method validation was performed according to the FDA rules.
Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Determination of Azole Antifugals in Human Serum H. Brozmanova1,2; R. Urinovska1,2; P. Sistik1,2; I. Kacirova1,2; and M. Grundmann1 1 University of Ostrava, Ostrava, Czech Republic; and 2University Hospital Ostrava, Ostrava, Czech Republic Background: Azole antifugals are used for the prevention and in the treatment of invasive life threatening fungal infections. The most commonly administrated antifugal agents are the triazole compounds fluconazole, voriconazole, posaconazole and intraconazole. Therapeutic monitoring of the triazoles is recommended to assure sufficient and safe concentrations in serum Methods: A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of fluconazole (FLU), ketoconazole (KET), voriconazole (VOR), posaconazole (POS), itraconazole (ITR) and its active metabolite hydroxy- itraconazole (OH-ITR) was developed. 100 µL of 0.5 mol/L formic acid and 0.5 mL of acetonitrile with zinc sulphate were added to 200 µL of human serum. The mixture was vortex mixed and centrifuged in cold for 10 minutes. Supernatant was used for analysis. Chromatographic conditions were as follows: Column BEH C18 50x2.1, 1.7µm, mobile phase composed from water, acetonitrile, 2 mmol/L ammonium acetate and a 0.1% formic acid. Rate of mobile phase was 0.4 mL /min, temperature of column was maintained at 50 oC and time of analysis was 5 minutes. Ascomycin D was used as an internal standard. Results: Calibration curves were used in the range of 0.1-100 mg/L for FLU and 0.01-10 mg/L for KET, VOR, POS, ITR and its metabolite OH-ITR. Coefficient of variations (intraassay and interassay) was found between 1.7-10.1 % and recovery from 86.3 to 111.1 %. Conclusions: New LC-MS/MS method for analysis of azole antifugals concentrations was developed and validated. This method is fast and precise with simple sample extraction and has been introduced into routine therapeutic drug monitoring.
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Clinical Therapeutics Liquid Chromatography-Tandem Mass Spectrometry Method for Determination of Gentamicin Concentrations and Comparison with Two Immunoassay Methods (Chemiluminiscent Assay a Polarization Fluoroimmunoassay) H. Brozmanova1,2; R. Urinovska2; P. Sištik2; I. Kacirova1,2; and M. Grundmann1 1 University of Ostrava, Ostrava, Czech Republic; and 2University Hospital Ostrava, Ostrava, Czech Republic Background: Gentamicin belongs to aminoglycoside antibiotics. Therapeutic drug monitoring (TDM) of gentamicin is recommended for all patients to assure both sufficient and safe concentrations in blood. Gentamicin is composed from a mixture of three drugs (C1, C1A and C2A +C2) with the basic share as follows: C1 25-50%, C1A 10-35% and C2A + C2 25-55%. Gentamicin concentrations are preferably measured using immunoanalytical assays. Methods: A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with simple sample extraction and a relatively short time of gentamicin analysis was developed and validated. 50 µL of serum was precipitated using acetonitrile and formic acid. A RP BEH C18, 1.7 µm, 2.1 x 50 mm column maintained at 30oC and tobramycin as internal standard were used. Mass detection was performed in positive electrospray mode. The results were compared with analyses of polarization fluoroimmunoassay (FPIA) method (Abbott AxSYM) and a chemiluminiscent assay (Advia Centauer, Siemens). Passing-Bablok regression analysis and Bland-Altman analysis were used to compare gentamicin concentrations. Results: Calibration curve was linear in the range of 0.1-50 mg/L. Recovery was 91.6-102.0% with a coefficient of variations of 1.4-8.4% for single types of gentamicin. The sum of gentamicin concentrations correlated significantly with both immunoanylatical assays. Conclusions: Presented LC-MS/MS method is fast and precise with simple sample extraction and can be applied for routine TDM of gentamicin.
Liquid Chromatography-Tandem Mass Spectrometry Method for Tdm of Vancomycin and Comparison with Results of Polarization Fluoroimmunoassay H. Brozmanova1,2; I. Kacirova1,2; R. Urinovska1,2; P. Sistik1,2; and M. Grundmann1 1 Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic; and 2University Hospital Ostrava, Ostrava, Czech Republic Background: Vancomycin is a glycopeptide antibiotic with a strong bactericidal activity used for the treatment of serious infections caused by gram-positive bacteria including methicillin-resistant Staphylococcus aureus. Therapeutic drug monitoring (TDM) of vancomycin is highly valuable due to the large interpatient and intra patient variability of pharmacokinetics. Methods: A new liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with simple sample extraction and a relatively short time of vancomycin analysis was developed and validated. 50 µL of serum was precipitated using 33% trichloroacetic acid, and NH4OH was added to increase pH before analysis. A RP BEH C18, 1.7 µm, 2.1 x 50 mm column maintained at 30oC and tobramycin as internal standard were used. Mass detection was performed in positive electrospray mode. The results were compared with analyses of polarization fluoroimmunoassay (FPIA) method (Abbott AxSYM). Subjects were divided into three groups according to serum creatinine levels (normal 53.5±19.1, 150.2±48.4 and 471.7±124.7 in dialyzed
e86
patients). Passing-Bablok regression analysis and Bland-Altman analysis were used to compare vancomycin concentrations. Results: Calibration curve was linear in the range of 0.1-100 mg/L. Recovery was 98.2-104.9% with a coefficient of variations of 1.77.2%. Vancomycin concentrations from dialyzed patients with the highest serum creatinine levels were about 14% greater than results from the FPIA assay. Conclusions: Presented LC-MS/MS method is fast and precise with simple sample extraction. These analytical conditions enable to receive the vancomycin concentrations early and along with interpretation of clinical pharmacologist make the dosage adjustment before the administration of the next vancomycin dose.
Improved Clinical Outcomes in paediatric Epileptic Patients on Lamotrigine therapy after implementation of Therapeutic drug monitoring B. Koristkova1,2; M. Grundmann1; I. Kacirova1,2; and H. Brozmanova1,2 1 University of Ostrava, Ostrava, Czech Republic; and 2University Hospital Ostrava, Ostrava, Czech Republic Background: Therapeutic drug monitoring (TDM) of lamotrigine has been recommended. Lamotrigine elimination by UGT is sensitive to induction and inhibition. Concomitant therapy with both enzyme inducers and inhibitors was described to be fully or partially compensated. The aim of our study was to analyse the impact of TDM on clinical outcomes of patients and importance of possible drug interactions, especially in triple combinations of antiepileptic drugs. Methods: During the period of 2001-2015 1308 pre-dose samples were taken from 430 patients < 15 years old as part of routine TDM. Drug interactions were evaluated using calculation of lamotrigine clearance. Mann-Whitney U-test for median values; χ 2-test for incidence of seizures, adverse drug reactions (ADRs) and distribution of plasma levels according to therapeutic range (TR) of 3-14 mg/L were calculated with aid of Prism 5.0, GraphPad Software. Results: Only 61% of samples reached TR during 2001-2005, compared to 74-75% during 2006-2015. TR was exceeded in 2% of cases in monotherapy, and in 6-7% of cases in combination therapy. ADRs were reported in 22 of cases (2%), more frequently in bi- and triple therapy. Seizures occurred more often daily and monthly during the first period, in patients with levels below TR, and in two or three antiepileptic drugs in combination. Carbamazepine and topiramate in bitherapies increased clearance of lamotrigine by 200% and 24%. Valproic acid decreased lamotrigine clearance by 53% in bitherapy, by 50% and 56% in triple therapy with levetiracetam and topiramate but only by 21% in triple therapy with carbamazepine. Levetiracetam had no effect on lamotrigine clearance. Conclusions: Long-term provided TDM led to decreased of seizure frequency in paediatric epileptic patients on lamotrigine therapy. The inhibitive effect of valproate was only partially decreased by carbamazepine.
Drug Interaction Between Clarithromycin And Tacrolimus – A Case Report B. Koristkova1,2; M. Grundmann1; I. Kacirova1,2; and R. Urinovska1,2 1 University of Ostrava, Ostrava, Czech Republic; and 2University Hospital Ostrava, Ostrava, Czech Republic A 16-year-old man (66 kg, 175 cm) after preemptive kidney transplantation from living donor (mother) in June 2017, was treated with tacrolimus (Prograf®) 1.5 mg twice daily (b.i.d.) and mycophenolate
Volume 39 Number 8S