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Pharmacokinetics of Ssri After Roux-En-Y-Gastric-Bypass—Review of The Literature and Case Study
Posters mofetil (Cellcept ®) 500 mg b.i.d. Blood levels of tacrolimus were 7.5 and 7.2 ng/mL on January 5th and 10th 2017, respectively. Mycophenolate blood levels fluctuated between 0.2 to 4.5 mg/L during January - February 2017. Because of diarrhea caused by Camphylobacter jejuni, clarithromycin (Klacid®) was given in doses 500 mg b.i.d since January 12th 2017. To prevent elevation of tacrolimus level due to expected drug interaction, the dosage of tacrolimus was lowered to 1 mg b.i.d. Despite of this, the level of tacrolimus reached to 43.0 ng/mL on January 16th. Although the evening dose was excluded, the level remained 31.0 and 46.8 ng/mL, respectively before and after the morning dose on January 17th. The treatment with claritromycin was discontinued (on day 5th) and tacrolimus was temporally excluded. Tacrolimus levels in following days were: 23.4 (Jan 18th), 13.3 (Jan 19th) and 5.8 ng/mL (Jan 20th), respectively. Tacrolimus was added to therapy using following doses: 0.5 mg on Jan 20th and 1 mg b.i.d on Jan 21st and 22nd. On Jan 23rd the pre-dose tacrolimus level dropped to 3.8 ng/mL. As inhibitive effect of claritromycin disappeared, tacrolimus 1.5 mg b.i.d was given. Tacrolimus level of 5.1 ng/mL was found during routine control on Feb 9th. Decline of tacrolimus level was simulated with the aid of MW-Pharm 3.30 software. As no population data were available in this version, the nitrazepam model was used successfully. Tacrolimus model in the latest version of MW-Pharm 4.0 (1.3.5.558 version) was tested a posteriori but the model was not able to consider fluctuation of metabolism of tacrolimus due to drug interaction after the clarithromycin withdrawal.
Nicotine Metabolite Ratio in Smokers: A Real World Experience S. Fogli1; B. Polini1; L. Carrozzi2; F. Pistelli2; G. Puppo2; A. Palla2; A. Saba1; R. Zucchi1; M. Del Re2; and R. Danesi1 1 University of Pisa, Pisa, Italy; and 2University Hospital of Pisa, Italy Background: The ratio of two metabolites derived from nicotine smoking, 3’-hydroxycotinine (3HC) and cotinine (COT) (nicotine metabolite ratio, NMR), reflects the activity of the liver enzyme CYP2A6 and it has been shown to predict response to smoking cessation drugs in clinical trials. The aim of the present study is to facilitate translation of study findings in the real life clinical practice. Methods: We carried out a clinical validation of a mass spectrometerbased method for measuring the NMR in both plasma and saliva samples obtained from 71 smokers attending the Smoking Cessation Centre of the University Hospital of Pisa. We also performed a realtime PCR analysis for fast genotyping of CYP2A6. Results: The mean COT and 3HC concentrations in plasma were 260.3 and 80.2 ng/ml, respectively, whereas those in saliva were 298.3 and 137.3 ng/ml, respectively. Linear regression analyses showed a significant (p< 0.001) relationship among metabolites levels measured in plasma and saliva with correlation coefficients (r) of 0.951 for COT, 0.841 for 3HC, and 0.694 for NMR. While the mean NMR values for slow metabolizers (NMR< 0.31) were superimposable in plasma and saliva samples (i.e., 0.21±0.01), they differed in those smokers having a normal/fast metabolizer phenotype (0.39±0.01 and 0.48±0.02, respectively). The percentages of slow metabolizers were 42.8% in plasma and 22.4% in saliva samples. The specific CYP2A6*9 variant allele (c.-48T> G) in the CYP2A6 locus associated with decreased nicotine metabolism was identified in 36% of smokers, including heterozygous (30%) and homozygous (6%) genotypes. Conclusions: These findings provide evidence that salivary NMR measures were comparable to plasma levels in a real-life setting. Nonetheless, the reliability of a saliva test for measuring the phenotype for nicotine metabolic status in individual smokers needs further investigation.
August 2017
Pharmacokinetics of Valproate and Lamotrigine Combined Therapy in Pregnancy and its Effect on the Newborn – A Case Report E. Rumpel1; I. Kacirova1,2; and M. Grundmann1 1 University of Ostrava, Ostrava, Czech Republic; and 2University Hospital Ostrava, Ostrava, Czech Republic Background: In a previous paper we found that birth length and weight were inversely related to maternal and umbilical cord levels of valproate (VPA), but not to dose. In a case report we tried to determine, whether it is possible to use this data for prediction of fetal plasma concentrations during pregnancy. Methods: A 30-year-old woman (59 kg prior to pregnancy) was treated by a combined therapy of VPA (Orfiril long®, 800 mg/day) and lamotrigine (Lamictal®, 200mg/day) for pseudoabsences. Plasma levels of both drugs were measured at steady-state before, during and after pregnancy and also during the delivery. Levels of VPA were measured by gas chromatography and levels of lamotrigine (LTG) by high performance liquid chromatography. Apparent oral clearance (Cl) was calculated for both drugs: daily dose (mg/kg)/serum concentration (mg/L). Results: Drug levels before the pregnancy were 67.9 mg/L for VPA and 15.2 mg/L for LTG. By the time of delivery both levels have decreased to 32.2 mg/L for VPA and 6 mg/L for LTG in maternal serum. Values measured in umbilical cord were 41.6 mg/L (129% of maternal value) for VPA and 5.9 mg/L for LTG (100% of maternal value). Apparent oral clearance of VPA was increased by 171% (from 0.2 L/24 h to 0.54 L/24 h) and of LTG by 143% (from 0.22 L/24 h to 0.54 L/24 h) at the end of 3rd trimester. The birth length was 43 cm and weight 2.15 kg. Conclusions: The low total values of LTG clearance can be attributed to interaction with VPA. The difference between maternal levels and the levels in umbilical cord can be used for prediction of VPA fetal levels during the 1st trimester = 81 mg/L, which is possibly teratogenic and could explain the low birth length.
Pharmacokinetics of Ssri After Roux-EnY-Gastric-Bypass—Review of The Literature and Case Study M.H. Andresen; H. Lövborg; and Y. Böttiger Linköping university, Linköping, Sweden Background: The prevalence of obesity is growing; WHO reports that in 2014 13% of adults aged 18 years and over were obese. A growing number of patients are treated with surgery, laparoscopic Roux-en-Y Gastric Bypass (RYGB) being considered the gold standard. Because of changes in intestinal anatomy, changes in pharmacokinetics are to expect. The point prevalence of depression in Sweden is 5.2%; 20-50% of patients undergoing bariatric surgery in the US have a medical history of mood disorder. However, documentation for changes in pharmacokinetics of antidepressive agents of type selective serotonin reuptake inhibitors (SSRI) is sparse. Methods: Literature was reviewed using PubMed with search terms as follows: Biliopancreatic Diversion with Duodenal Switch, BPD/DS, gastric band, gastric sleeve, gastric bypass, roux-en-Y, bariatric surgery, SSRI, psychopharmacology, selective serotonin reuptake inhibitor[s] and the names of the individual agents. From the reference lists additional references were identified. Only English-language articles were included. Three patients, treated with sertraline, were included; serum concentrations were taken eight weeks before, three month after and twelve month after surgery.
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Clinical Therapeutics 5 ml blood samples were taken 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 24 hours after last intake of sertraline and analysed with LCMS/MS. Results: Five studies with 30 patients could be identified; 22 of them after RYGB. Methods, sampling, measurements and agents varied between studies making it difficult to draw conclusions from the material. One study with case-crossover-design shows, that concentrations of sertraline, venlafaxine and citalopram decline after surgery and rise to or over concentrations before surgery. Data from serum concentrations will be delivered. Conclusions: More research with comparable methods and studies clarifying the clinical consequences of the pharmacokinetic changes are needed to clarify amount and relevance of changes in pharmacokinetics of SSRI after bariatric surgery.
Comparison of MW-Pharm 3:30 and Mw-Pharm++—A Windows Version of Pharmacokinetic Software for Pk/Pd Monitoring T. Poruban1; B. Koristkova1,2; M. Grundmann1; and I. Kacirova1,2 University of Ostrava, Ostrava, Czech Republic; and 2University Hospital Ostrava, Ostrava, Czech Republic Background: MW-Pharm 3:30 (DOS) has been long-term used for PK/PD monitoring in therapeutic drug monitoring. The Windows version was introduced with larger spectrum of models available. The aim of this study was to compare differences of prediction of plasma levels of digoxin with the aid of both DOS and Windows version. Methods: 29 patients repeatedly examined for digoxin in 2016, mean age 67±20 years, body weight 72±27 kg, were treated with median dose 125 ng/day (94-125). The differences between plasma level measured and predicted by models “#digoxin_C1” (MW-Pharm++ 1.3.5.558) and “digoxin” (MW-Pharm 3:30) were compared. Statistical analysis was performed using GraphPad prism version 5.00 for Windows, GraphPad Software, San Diego California USA, Wilcoson signed rank test was applied. Results: There were no significant diffirences found between measured and predicted values by models “#digoxin_C1” (MW-Pharm++ 1.3.5.558) and “digoxin” (MW-Pharm 3:30). There were no significant diffirences found between measured and predicted values between models “#digoxin_C1” (MW-Pharm++ 1.3.5.558) and “digoxin” (MW-Pharm 3:30). Percentage prediction error (%pe) calculated as (predicted – measured)/measured between measured and predicted levels by model “#digoxin_C1” (MW-Pharm++ 1.3.5.558) was 3.17 %. Percentage prediction error (%pe) calculated as (predicted – measured)/measured between measured and predicted levels by model “digoxin” (MW-Pharm 3:30) was 0.17 %. Percentage prediction error (%pe) calculated as (predicted – measured)/measured between measured and predicted levels between those models was –0.19%. Conclusions: Both programmes are appropriate for TDM of digoxin. 1
The Challenge of Personalised Medicine and the Issue of Tki Resistance: A Rare Patient Case with Resistance to First and Second Generation TKIS G. Kostova Hematology Clinic, Medical Faculty, University In Skopje Background: Treatment with TKI has dramatically changed disease prognosis in patients with chronic myeloid leukemia, who now have normal life expectancy. TKI resistance, primary or acquired, is still a problem in the treatment of patients with chronic myeloid leukemia. Second and third generation TKIs have been used in patients with imatinib failure. Unfortunately, some patients are refractory to all
e88
available TKIs. Here we present a rare patient with chronic myeloid leukemia and resistance to imatinib and nilotinib. Case Presentation: 25-year old female patient has been diagnosed as having chronic myeloid leukemia during the evaluation for leukocytosis. Treatment was started with generic imatinib. Unfortunately, no major molecular response has been achieved and the initial hematological remission has been lost after 14 months of treatment. Resistance investigations revealed no bcr/abl mutations. Treatment with second generation TKI nilotinib achieved fast and deep molecular remission, which unfortunately has been sustained for less than six months. Again, resistance investigation revealed no bcr/abl mutations. Treatment with dasatinib has not been approached, because of no availability of the drug. The patient underwent HLA – matched sibling transplantation, but unfortunately died on sever hepatic GvHD two months after transplant procedure. Conclusions: Targeting a driver mutation, as bcr/abl in chronic myeloid leukemia has the greatest therapeutic potencial in the tailored therapy strategy.Bcr/abl point mutations, amplification of bcr/abl gene and increased expression of efflux drug transporters are the already known mechanisms for TKI failure in only half of the patients. Therefore, detailed further investigation of molecular resistance mechanisms is urgently needed for a successful targeted therapy in the future.
The Irrational Prescription of Medicines for Children in Ophthalmic Practice T. Uskenbaev1; U. Tilekeeva1; B. Yeraliyeva2; G. Boronbaeva2; and G. Erkinbekova2 1 Kyrgyz State Medical Academy, Bishkek, Kyrgyz Republic; and 2 Asfendiarov Kazakh National Medical University Despite progress made in recent years, it was noted that the need for more drugs, developed and tested specifically for children. Recently, in connection with the expansion of drug market, in particular, children’s medicines to doctors and parents is a difficult choice - whether the children need to take a wide range of medicines for these diseases? At the end of the last century, the WHO concerned about this issue, then its experts concluded that two-thirds of all medicines used in children value at all useless. One of the important issues - general-purpose medicines not intended for children (off-label) and non-registered for use in the pediatric medicines (unlicensed use). The purpose of research. To study the rationality use drugs in actual pediatric ophthalmic practice. Analysis of the medical records of 456 children with these ophthalmic pathology. Assessment indicator: the number of appointments “off-label” children, polypharmacy. 456 children received the drugs, the average load on 1 patient was 5.7. 693 assigned to the drug off label that was 29.8%, almost every third. Contraindications for use in children is the lack of data on the pharmacokinetic and pharmacodynamic parameters of medicines in children. Conclusion. In clinical practice ophthalmologists prescribe too many drugs - a high degree of polypharmacy and often unnecessary medication is contraindicated in children and unproven efficacy and safety. Conclusion. In clinical practice, ophthalmic doctors prescribe too many drugs - a high degree of polypharmacy and very often unnecessary drugs contraindicated to children with unproven efficacy and safety
Patient Knowledge of Non-Steroidal Anti-Inflammatory Drugs Use, Effects and Safety R. Rutkaityte1; S. Maciulskyte2; S. Stankeviciute2; and G. Gumbrevicius2
Volume 39 Number 8S
Nicotine Metabolite Ratio in Smokers: A Real World Experience S. Fogli1; B. Polini1; L. Carrozzi2; F. Pistelli2; G. Puppo2; A. Palla2; A. Saba1; R. Zucchi1; M. Del Re2; and R. Danesi1 1 University of Pisa, Pisa, Italy; and 2University Hospital of Pisa, Italy Background: The ratio of two metabolites derived from nicotine smoking, 3’-hydroxycotinine (3HC) and cotinine (COT) (nicotine metabolite ratio, NMR), reflects the activity of the liver enzyme CYP2A6 and it has been shown to predict response to smoking cessation drugs in clinical trials. The aim of the present study is to facilitate translation of study findings in the real life clinical practice. Methods: We carried out a clinical validation of a mass spectrometerbased method for measuring the NMR in both plasma and saliva samples obtained from 71 smokers attending the Smoking Cessation Centre of the University Hospital of Pisa. We also performed a realtime PCR analysis for fast genotyping of CYP2A6. Results: The mean COT and 3HC concentrations in plasma were 260.3 and 80.2 ng/ml, respectively, whereas those in saliva were 298.3 and 137.3 ng/ml, respectively. Linear regression analyses showed a significant (p< 0.001) relationship among metabolites levels measured in plasma and saliva with correlation coefficients (r) of 0.951 for COT, 0.841 for 3HC, and 0.694 for NMR. While the mean NMR values for slow metabolizers (NMR< 0.31) were superimposable in plasma and saliva samples (i.e., 0.21±0.01), they differed in those smokers having a normal/fast metabolizer phenotype (0.39±0.01 and 0.48±0.02, respectively). The percentages of slow metabolizers were 42.8% in plasma and 22.4% in saliva samples. The specific CYP2A6*9 variant allele (c.-48T> G) in the CYP2A6 locus associated with decreased nicotine metabolism was identified in 36% of smokers, including heterozygous (30%) and homozygous (6%) genotypes. Conclusions: These findings provide evidence that salivary NMR measures were comparable to plasma levels in a real-life setting. Nonetheless, the reliability of a saliva test for measuring the phenotype for nicotine metabolic status in individual smokers needs further investigation.
August 2017
Pharmacokinetics of Valproate and Lamotrigine Combined Therapy in Pregnancy and its Effect on the Newborn – A Case Report E. Rumpel1; I. Kacirova1,2; and M. Grundmann1 1 University of Ostrava, Ostrava, Czech Republic; and 2University Hospital Ostrava, Ostrava, Czech Republic Background: In a previous paper we found that birth length and weight were inversely related to maternal and umbilical cord levels of valproate (VPA), but not to dose. In a case report we tried to determine, whether it is possible to use this data for prediction of fetal plasma concentrations during pregnancy. Methods: A 30-year-old woman (59 kg prior to pregnancy) was treated by a combined therapy of VPA (Orfiril long®, 800 mg/day) and lamotrigine (Lamictal®, 200mg/day) for pseudoabsences. Plasma levels of both drugs were measured at steady-state before, during and after pregnancy and also during the delivery. Levels of VPA were measured by gas chromatography and levels of lamotrigine (LTG) by high performance liquid chromatography. Apparent oral clearance (Cl) was calculated for both drugs: daily dose (mg/kg)/serum concentration (mg/L). Results: Drug levels before the pregnancy were 67.9 mg/L for VPA and 15.2 mg/L for LTG. By the time of delivery both levels have decreased to 32.2 mg/L for VPA and 6 mg/L for LTG in maternal serum. Values measured in umbilical cord were 41.6 mg/L (129% of maternal value) for VPA and 5.9 mg/L for LTG (100% of maternal value). Apparent oral clearance of VPA was increased by 171% (from 0.2 L/24 h to 0.54 L/24 h) and of LTG by 143% (from 0.22 L/24 h to 0.54 L/24 h) at the end of 3rd trimester. The birth length was 43 cm and weight 2.15 kg. Conclusions: The low total values of LTG clearance can be attributed to interaction with VPA. The difference between maternal levels and the levels in umbilical cord can be used for prediction of VPA fetal levels during the 1st trimester = 81 mg/L, which is possibly teratogenic and could explain the low birth length.
Pharmacokinetics of Ssri After Roux-EnY-Gastric-Bypass—Review of The Literature and Case Study M.H. Andresen; H. Lövborg; and Y. Böttiger Linköping university, Linköping, Sweden Background: The prevalence of obesity is growing; WHO reports that in 2014 13% of adults aged 18 years and over were obese. A growing number of patients are treated with surgery, laparoscopic Roux-en-Y Gastric Bypass (RYGB) being considered the gold standard. Because of changes in intestinal anatomy, changes in pharmacokinetics are to expect. The point prevalence of depression in Sweden is 5.2%; 20-50% of patients undergoing bariatric surgery in the US have a medical history of mood disorder. However, documentation for changes in pharmacokinetics of antidepressive agents of type selective serotonin reuptake inhibitors (SSRI) is sparse. Methods: Literature was reviewed using PubMed with search terms as follows: Biliopancreatic Diversion with Duodenal Switch, BPD/DS, gastric band, gastric sleeve, gastric bypass, roux-en-Y, bariatric surgery, SSRI, psychopharmacology, selective serotonin reuptake inhibitor[s] and the names of the individual agents. From the reference lists additional references were identified. Only English-language articles were included. Three patients, treated with sertraline, were included; serum concentrations were taken eight weeks before, three month after and twelve month after surgery.
e87
Clinical Therapeutics 5 ml blood samples were taken 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 24 hours after last intake of sertraline and analysed with LCMS/MS. Results: Five studies with 30 patients could be identified; 22 of them after RYGB. Methods, sampling, measurements and agents varied between studies making it difficult to draw conclusions from the material. One study with case-crossover-design shows, that concentrations of sertraline, venlafaxine and citalopram decline after surgery and rise to or over concentrations before surgery. Data from serum concentrations will be delivered. Conclusions: More research with comparable methods and studies clarifying the clinical consequences of the pharmacokinetic changes are needed to clarify amount and relevance of changes in pharmacokinetics of SSRI after bariatric surgery.
Comparison of MW-Pharm 3:30 and Mw-Pharm++—A Windows Version of Pharmacokinetic Software for Pk/Pd Monitoring T. Poruban1; B. Koristkova1,2; M. Grundmann1; and I. Kacirova1,2 University of Ostrava, Ostrava, Czech Republic; and 2University Hospital Ostrava, Ostrava, Czech Republic Background: MW-Pharm 3:30 (DOS) has been long-term used for PK/PD monitoring in therapeutic drug monitoring. The Windows version was introduced with larger spectrum of models available. The aim of this study was to compare differences of prediction of plasma levels of digoxin with the aid of both DOS and Windows version. Methods: 29 patients repeatedly examined for digoxin in 2016, mean age 67±20 years, body weight 72±27 kg, were treated with median dose 125 ng/day (94-125). The differences between plasma level measured and predicted by models “#digoxin_C1” (MW-Pharm++ 1.3.5.558) and “digoxin” (MW-Pharm 3:30) were compared. Statistical analysis was performed using GraphPad prism version 5.00 for Windows, GraphPad Software, San Diego California USA, Wilcoson signed rank test was applied. Results: There were no significant diffirences found between measured and predicted values by models “#digoxin_C1” (MW-Pharm++ 1.3.5.558) and “digoxin” (MW-Pharm 3:30). There were no significant diffirences found between measured and predicted values between models “#digoxin_C1” (MW-Pharm++ 1.3.5.558) and “digoxin” (MW-Pharm 3:30). Percentage prediction error (%pe) calculated as (predicted – measured)/measured between measured and predicted levels by model “#digoxin_C1” (MW-Pharm++ 1.3.5.558) was 3.17 %. Percentage prediction error (%pe) calculated as (predicted – measured)/measured between measured and predicted levels by model “digoxin” (MW-Pharm 3:30) was 0.17 %. Percentage prediction error (%pe) calculated as (predicted – measured)/measured between measured and predicted levels between those models was –0.19%. Conclusions: Both programmes are appropriate for TDM of digoxin. 1
The Challenge of Personalised Medicine and the Issue of Tki Resistance: A Rare Patient Case with Resistance to First and Second Generation TKIS G. Kostova Hematology Clinic, Medical Faculty, University In Skopje Background: Treatment with TKI has dramatically changed disease prognosis in patients with chronic myeloid leukemia, who now have normal life expectancy. TKI resistance, primary or acquired, is still a problem in the treatment of patients with chronic myeloid leukemia. Second and third generation TKIs have been used in patients with imatinib failure. Unfortunately, some patients are refractory to all
e88
available TKIs. Here we present a rare patient with chronic myeloid leukemia and resistance to imatinib and nilotinib. Case Presentation: 25-year old female patient has been diagnosed as having chronic myeloid leukemia during the evaluation for leukocytosis. Treatment was started with generic imatinib. Unfortunately, no major molecular response has been achieved and the initial hematological remission has been lost after 14 months of treatment. Resistance investigations revealed no bcr/abl mutations. Treatment with second generation TKI nilotinib achieved fast and deep molecular remission, which unfortunately has been sustained for less than six months. Again, resistance investigation revealed no bcr/abl mutations. Treatment with dasatinib has not been approached, because of no availability of the drug. The patient underwent HLA – matched sibling transplantation, but unfortunately died on sever hepatic GvHD two months after transplant procedure. Conclusions: Targeting a driver mutation, as bcr/abl in chronic myeloid leukemia has the greatest therapeutic potencial in the tailored therapy strategy.Bcr/abl point mutations, amplification of bcr/abl gene and increased expression of efflux drug transporters are the already known mechanisms for TKI failure in only half of the patients. Therefore, detailed further investigation of molecular resistance mechanisms is urgently needed for a successful targeted therapy in the future.
The Irrational Prescription of Medicines for Children in Ophthalmic Practice T. Uskenbaev1; U. Tilekeeva1; B. Yeraliyeva2; G. Boronbaeva2; and G. Erkinbekova2 1 Kyrgyz State Medical Academy, Bishkek, Kyrgyz Republic; and 2 Asfendiarov Kazakh National Medical University Despite progress made in recent years, it was noted that the need for more drugs, developed and tested specifically for children. Recently, in connection with the expansion of drug market, in particular, children’s medicines to doctors and parents is a difficult choice - whether the children need to take a wide range of medicines for these diseases? At the end of the last century, the WHO concerned about this issue, then its experts concluded that two-thirds of all medicines used in children value at all useless. One of the important issues - general-purpose medicines not intended for children (off-label) and non-registered for use in the pediatric medicines (unlicensed use). The purpose of research. To study the rationality use drugs in actual pediatric ophthalmic practice. Analysis of the medical records of 456 children with these ophthalmic pathology. Assessment indicator: the number of appointments “off-label” children, polypharmacy. 456 children received the drugs, the average load on 1 patient was 5.7. 693 assigned to the drug off label that was 29.8%, almost every third. Contraindications for use in children is the lack of data on the pharmacokinetic and pharmacodynamic parameters of medicines in children. Conclusion. In clinical practice ophthalmologists prescribe too many drugs - a high degree of polypharmacy and often unnecessary medication is contraindicated in children and unproven efficacy and safety. Conclusion. In clinical practice, ophthalmic doctors prescribe too many drugs - a high degree of polypharmacy and very often unnecessary drugs contraindicated to children with unproven efficacy and safety
Patient Knowledge of Non-Steroidal Anti-Inflammatory Drugs Use, Effects and Safety R. Rutkaityte1; S. Maciulskyte2; S. Stankeviciute2; and G. Gumbrevicius2
Volume 39 Number 8S