Papers by Synnöve Lindemalm
Advances in Experimental Medicine and Biology, 1998
Seventeen patients with CLL were treated with oral 2-chloro-2'-deoxyadenosine (cladribine... more Seventeen patients with CLL were treated with oral 2-chloro-2'-deoxyadenosine (cladribine, CdA, 10 mg/m2) on 3 consecutive days and the pharmacokinetic parameters of CdA in patient plasma and its intracellular nucleotides (CdAMP, CdATP) in circulating leukemic cells were studied after the last dose intake and up to 72 h thereafter. The median terminal half life (t1/2) of CdA in plasma was 21.1 h and the area under the curve (AUC) was median 1.2 microMh. The median t1/2 was 14.6 h for CdAMP and 9.7 h for CdATP. The AUC of CdATP in leukemic cells is lower than the AUC of CdAMP (median ratio 0.60). There was no correlation between cellular CdATP and plasma CdA concentrations or dCK activity. The clinical response was related to higher Cmax values for plasma CdA (p = 0.05) and higher products of dCK activity and CdA Cmax of plasma (p = 0.02). The activity of dCK alone was not related to the clinical outcome in this patient group. The results suggest that further steps in the mechanism of action of CdA beyond its bioactivation may be more important, e.g. the extent of DNA fragmentation or the ability of the leukemic cell to go into apoptosis, than the concentration of CdA nucleotides alone.
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BMC pharmacology, Jan 9, 2005
The nucleoside analog cladribine is used for the treatment of a variety of indolent B- and T-cell... more The nucleoside analog cladribine is used for the treatment of a variety of indolent B- and T-cell lymphoid malignancies. The primary aim of the study was to evaluate the population distribution of pharmacokinetic parameters in patients undergoing treatment with cladribine and to detect the influence of different covariates on the pharmacokinetic parameters. This pharmacokinetic study presents the results of a retrospective population pharmacokinetic analysis based on pooled data from 161 patients, who were given cladribine in different administration routes in various dosing regimens. The plasma concentrations of cladribine were determined by reversed-phase high-performance liquid chromatography using a solid phase extraction with a limit of quantitation of 1 nM using 1 mL of plasma. A three compartment structural model best described the disposition of cladribine. Clearance was found to be 39.3 L/hour, with a large interindividual variability. The half-life for the terminal phase w...
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Pharmaceuticals
This is a registry-based study with the aim of describing and comparing the frequency of manipula... more This is a registry-based study with the aim of describing and comparing the frequency of manipulations of solid oral and rectal medicines in 2009 and 2019 at inpatient units and an emergency department in a paediatric hospital within a Swedish university hospital. All patients aged 1 month–18 years with oral or rectal administrations were included. In total, 140,791 oral and rectal administrations were included in 2009, and 167,945 oral and rectal administrations were included in 2019. The frequency of patients receiving at least one manipulated oral medicine decreased between the study years, both in inpatient units and in the emergency department (from 19% to 17%, p = 0.0029 and from 11% to 5%, p < 0.0001, respectively). The frequency of patients receiving a manipulated rectal medicine also decreased between the study years, both in inpatient units and in the emergency department (from 22% to 10%, p < 0.0001 and from 35% to 7% 2019, p < 0.0001, respectively). The results ...
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Journal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners, 2022
BACKGROUND Long term treatment of pediatric patients with oral anticancer drugs (OADs) requires t... more BACKGROUND Long term treatment of pediatric patients with oral anticancer drugs (OADs) requires the parents/caregivers to prepare the drug at home. The handling procedures in the home setting are, however, not regulated by Swedish law and the parents are often left without guidance on how to handle OADs in a safe way. AIM The aim of this study was to increase understanding of how OADs are handled by parents/caregivers in the home setting before and after an intervention. METHODS Parents of pediatric cancer patients were observed and videotaped during their handling of OADs in the home setting before and after the intervention. During the intervention, the parents were provided with written instructions, movie clips and practical training on handling the OADs. Four checklists were used to compare and score the four handling procedures (measuring an oral suspension, cutting tablets, dissolving tablets, and opening capsules) for each parent before and after the intervention. RESULTS Th...
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International Journal of Pediatrics and Adolescent Medicine, 2020
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Section 5: Patient safety and quality assurance, 2018
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Pharmaceutical Methods, 2016
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Clinical cancer research : an official journal of the American Association for Cancer Research, 1998
The pharmacokinetic parameters of cladribine (CdA) in patient plasma and its intracellular nucleo... more The pharmacokinetic parameters of cladribine (CdA) in patient plasma and its intracellular nucleotides CdA 5'-monophosphate (CdAMP) and CdA 5'-triphosphate (CdATP) were delineated in circulating leukemia cells in 17 patients with chronic lymphocytic leukemia, after the last dose intake and up to 72 h thereafter. Patients were treated with 10 mg/m2 CdA p.o. on 3 consecutive days. A novel and specific ion-pair liquid chromatographic method, which separates the intracellular CdA nucleotides, was used. The area under the concentration versus time curve (AUC) of CdAMP in leukemia cells was generally higher (median, 47 micromol/liter x h) than the AUC of CdATP (median, 22 micromol/liter x h); however, in some patients (3 of 17), the reverse relationship was seen. The median ratio between the AUC values for CdATP and CdAMP was 0.60 (95% confidence interval, 0.4-1.0). The median half-life (t(1/2)) of CdAMP was 15 h, and that of CdATP was 10 h. The median terminal t(1/2) of CdA in pl...
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Pharmacoepidemiology and Drug Safety, 2011
To evaluate drug and indication specific off-label use in paediatrics, applied to ciprofloxacin (... more To evaluate drug and indication specific off-label use in paediatrics, applied to ciprofloxacin (CPFX) in cholangitis. We collected four different sets of data for an off-label drug use evaluation. (1) Literature review from medical journals, (2) the use and safety profile from the whole Swedish paediatric population by extracting data from national registers, (3) locally performed retrospective drug chart reviews, and (4) interviews regarding paediatric patients with CPFX treated cholangitis. The literature reviews show a lack of information for paediatric use of CPFX in cholangitis. The prescribing of CPFX to Swedish children has grown over the last decade and generated a small number of reports for adverse drug reactions. In our local biliary atresia population 32 patients had suffered from at least one episode of cholangitis and 13 patients had been prescribed CPFX. The dosing strategy had an empirical prescribing approach, since monitoring of bacterial resistance and efficacy is difficult in the biliary ducts. No clear relationship was seen between dosing and age/weight. Reports of suspected side effects could not be found in the retrospective chart reviews. The interviews show that the existing dosage forms are well accepted. This drug use evaluation creates awareness of the off-label situation. The international and national data are sparse for the paediatric use of CPFX in cholangitis. Locally we have highlighted a heterogeneous dosing strategy of CPFX, drug/drug interactions, and the need to monitor and report the risk of short- and long-term adverse drug reactions.
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Clinical Cancer Research
The pharmacokinetic parameters of cladribine (CdA) in patient plasma and its intracellular nucleo... more The pharmacokinetic parameters of cladribine (CdA) in patient plasma and its intracellular nucleotides CdA 5'-monophosphate (CdAMP) and CdA 5'-triphosphate (CdATP) were delineated in circulating leukemia cells in 17 patients with chronic lymphocytic leukemia, after the last dose intake and up to 72 h thereafter. Patients were treated with 10 mg/m2 CdA p.o. on 3 consecutive days. A novel and specific ion-pair liquid chromatographic method, which separates the intracellular CdA nucleotides, was used. The area under the concentration versus time curve (AUC) of CdAMP in leukemia cells was generally higher (median, 47 micromol/liter x h) than the AUC of CdATP (median, 22 micromol/liter x h); however, in some patients (3 of 17), the reverse relationship was seen. The median ratio between the AUC values for CdATP and CdAMP was 0.60 (95% confidence interval, 0.4-1.0). The median half-life (t(1/2)) of CdAMP was 15 h, and that of CdATP was 10 h. The median terminal t(1/2) of CdA in pl...
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Abstract Aim: To study tolerance and acceptance in pediatric patients for MedCoat® in-situ coatin... more Abstract Aim: To study tolerance and acceptance in pediatric patients for MedCoat® in-situ coating of tablets/capsules. Methods: A non-randomized intervention study was performed at Astrid Lindgren Children´s Hospital, Karolinska University Hospital. A total number of 78 pediatric patients were included in the study (43 females and 35 males). The ability of patients (median age 9 years; range 2-17 years) to swallow tablets/capsules was evaluated by questionnaires. Results: Swallowing ability and palatability was improved by in-situ coating. Sixty-six out of 77 pediatric patients (86%; 95%CI: 76 to 93%) reported facilitated drug treatment after in-situ coating. Conclusion: Drug therapy was facilitated and in-situ coating was well accepted and tolerated for most pediatric patients.
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Acta Paediatrica, 2015
ABSTRACT Getting children to swallow tablets and capsules is a challenge and factors that influen... more ABSTRACT Getting children to swallow tablets and capsules is a challenge and factors that influence their ability to swallow include taste, smell and texture. The aim of this study was to explore how well paediatric patients tolerated and accepted the MedCoat(®) in-situ coating for tablets and capsules. A non-randomised intervention study was performed at the Astrid Lindgren Children&#39;s Hospital, Karolinska University Hospital, Sweden. We identified 78 paediatric patients - 43 females and 35 males - who had problems swallowing tablets and capsules and evaluated their abilities with questionnaires. The median age of the patients was nine-years-old and the range was two to 18-years-old. Swallowing ability and palatability was improved by in-situ coating. The results showed that 66 out of 77 paediatric patients (86%, 95% confidence interval: 76 to 93%) were able to take the drugs they had been prescribed after in-situ coating. Swallowing improved in 87% of cases and palatability improved in 85%. A study of 77 paediatric patients with a median age of nine years, and a range of two to 18 years, found that 86% were able to take the tablets and capsules they had been prescribed after they were coated with the MedCoat. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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BMC health services research, Jan 21, 2014
BackgroundLittle is known about adverse events (AEs) in pediatric patients. Record review is a co... more BackgroundLittle is known about adverse events (AEs) in pediatric patients. Record review is a common methodology for identifying AEs, but in pediatrics the record review tools generally have limited focus. The aim of the present study was to develop a broadly applicable record review tool to identify AEs in pediatric inpatients.MethodsUsing a broad literature review and expert opinion with a modified Delphi process, a pediatric trigger tool with 88 triggers, definitions, and descriptions including AE preventability decision support was developed and tested in a random sample of 600 hospitalized pediatric patients admitted in 2010 to a single university children¿s hospital. Four registered nurse-physician teams performed complete two-stage retrospective reviews of 150 records each from either neonatal, surgical/orthopedic, medicine, or emergency medicine units.ResultsRegistered nurse review identified 296 of 600 records with triggers indicating potential AEs. Records (n¿=¿121) with ...
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Lakartidningen
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Haematologica, 2003
Clofarabine (CAFdA), one of the newer nucleoside drugs is undergoing a phase II clinical trial fo... more Clofarabine (CAFdA), one of the newer nucleoside drugs is undergoing a phase II clinical trial for the treatment of pediatric refractory/relapsed acute myeloid and lymphocytic leukemia. Although CAFdA is structurally similar to the clinically established analogs fludarabine and cladribine (CdA), its metabolism and mechanism of actions are significantly different. The present study investigates the in vitro cytotoxicity of CAFdA and CdA in mononuclear cells isolated from 52 patients with chronic lymphocytic (CLL) and acute myeloid leukemia (AML). We incubated the leukemic cells with drugs for 48 hours and cytotoxicity was then evaluated by the MTT dye assay. We also determined the levels of deoxycytidine and deoxyguanosine kinase with radio-chemical substrate-based assays and used a high performance liquid chromatographic method to measure cellular nucleotides in leukemia cells after 2 hours' incubation. Using equimolar concentrations of CAFdA and CdA, the in vitro cytotoxicity f...
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Leukemia Research, 2001
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Journal of Human Lactation, 2009
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European Journal of Pediatrics, 2011
We have used three different sources to estimate the use of drugs sold over the counter (OTC) by ... more We have used three different sources to estimate the use of drugs sold over the counter (OTC) by the Swedish paediatric population during 2007-2008 as part of a European evaluation initiated by the European Medicines Agency. An estimation of the paediatric use from the total numbers of over-the-counter drugs (OTCD) packages sold by Swedish pharmacies and analyses of two separate questionnaires directed towards a population of 11- to 14-year-old children and another towards visitors to one of the paediatric emergency wards in Stockholm County were included in the study. In Sweden, 1.25 OTC packages are sold quarterly per child (0-18 years), and the children in both questionnaire studies use, on average, 0.9 OTC substances. Sixty-five percent of the children visiting an emergency ward and 67% of the 13-year-old Stockholm inhabitants had used at least one OTCD. OTCD use among children is common. Interpretation of OTCD data must be done carefully since questions with regard to OTCD use is subject to recall bias and the number of packages sold to children is hypothesised through a conversion factor.
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European Journal of Clinical Pharmacology, 2011
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Papers by Synnöve Lindemalm