Category Archives: Br J Clin Pharmacol

The impact of CYP2D6 mediated drug-drug interaction: a systematic review on a combination of metoprolol and paroxetine/fluoxetine.

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The impact of CYP2D6 mediated drug-drug interaction: a systematic review on a combination of metoprolol and paroxetine/fluoxetine.
Br J Clin Pharmacol. 2018 Sep 24;:
Authors: Bahar MA, Kamp J, Borgs… Continue reading

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Blood pressure lowering effects of sulodexide depend on albuminuria severity: Post hoc analysis of the sulodexide microalbuminuria and macroalbuminuria studies.

Blood pressure lowering effects of sulodexide depend on albuminuria severity: Post hoc analysis of the sulodexide microalbuminuria and macroalbuminuria studies.

Br J Clin Pharmacol. 2016 Jul 14;

Authors: Olde Engberink RH, Heerspink HJ, de Zeeuw D, Vogt L

Abstract
AIMS: It has been suggested that sulodexide is able to lower blood pressure (BP). This may be attributed to sulodexide’s ability to restore the endothelial surface layer (ESL). As ESL perturbation is known to be related to the degree of kidney damage, we investigated whether albuminuria, reflecting ESL status, modified the BP lowering potential of sulodexide.
METHODS: A post hoc analysis of the double-blind randomized placebo-controlled sulodexide microalbuminuria (Sun-MICRO) and macroalbuminuria studies (Sun-MACRO) including 1,056 microalbuminuric and 843 macroalbuminuric subjects with type 2 diabetes receiving maximal tolerated renin-angiotensin inhibitor therapy. We compared the effect of placebo and sulodexide on systolic BP (SBP) among albuminuria groups.
RESULTS: Analysis of covariance including data from both trials showed that baseline urine albumin-to-creatinine ratio (UACR) was the only modifier of the SBP response (interaction with treatment p = 0.001). In subjects with an UACR >1,000 mg/g, sulodexide lowered SBP by 4.6 mmHg (95% CI: 3.6-5.6, p < 0.001) compared to placebo, whereas a 2.3 mmHg (95% CI: 0.9-3.7, p = 0.001) reduction was seen in subjects with an UACR 300-1000 mg/g. Sulodexide did not lower SBP in subjects with an UACR <300 mg/g (-0.2 mmHg, 95% CI -0.8-0.5, p = 0.60). SBP lowering effects were not accompanied by changes in body weight.
CONCLUSION: The BP reducing potency of sulodexide is modified by the degree of albuminuria in subjects with type 2 diabetes. As ESL status deteriorates with increasing albuminuria and nephropathy severity, this suggests that ESL restoration may represent a new target for BP treatment in subjects with diabetic nephropathy.

PMID: 27412828 [PubMed – as supplied by publisher]

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Evaluation of an oral uracil loading test to identify DPD-deficient patients using a limited sampling strategy.

Evaluation of an oral uracil loading test to identify DPD-deficient patients using a limited sampling strategy.

Br J Clin Pharmacol. 2015 Nov 9;

Authors: van Staveren MC, van Kuilenburg AB, Guchelaar HJ, Meijer J, Punt CJ, de Jong RS, Gelderblom H, Maring JG

Abstract
AIM(S): Dihydropyrimidine dehydrogenase (DPD) deficiency can lead to severe toxicity following 5FU or capecitabine (CAP) treatment. Uracil (U) can be used as a probe to determine the systemic DPD activity. This study was performed to assess the sensitivity and specificity of an U loading dose for detecting DPD deficiency.
METHODS: Cancer patients with Common Toxicity Score (CTC) grade III or IV toxicity after the first or second cycle of 5-FU or capecitabine treatment were asked to participate. Based on DPD activity in PBMCs, patients were divided in 2 groups: DPD activity in PBMCs < 5 nmol/mg*hr (deficient group) and ≥ 5 nmol/mg*hr. U 500 mg m(2) was administered orally and plasma concentrations of U and dihydrouracil (DHU) in plasma were determined. In the deficient group, PCR amplification of all 23 coding exons and flanking intronic regions of DPYD was performed. An U pharmacokinetic model was developed and used to determine Vmax of the DPD enzyme of each patient. Sensitivity and specificity of Vmax, U concentration and the U/DHU concentration ratio were determined.
RESULTS: 47 patients were included (19 DPD deficient, 28 DPD normal). Of the pharmacokinetic parameters investigated, a sensitivity and specificity of 80% and 98% respectively was obtained for the U/DHU ratio at t = 120 min.
CONCLUSIONS: The high sensitivity of the U/DHU ratio at t = 120 min for detecting DPD deficiency as defined by DPD activity in PBMCs, show that the oral U loading dose can effectively identify patients with reduced DPD activity.

PMID: 26551538 [PubMed – as supplied by publisher]

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The blood pressure lowering potential of sulodexide – a systematic review and meta-analysis.

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The blood pressure lowering potential of sulodexide – a systematic review and meta-analysis.

Br J Clin Pharmacol. 2015 Jul 15;

Authors: Olde Engberink RH, Rorije NM, Lambers Heerspink HJ, De Zeeuw D, Van Den Born BJ, Vogt L

Abstract
AIMS: Sulodexide is a highly purified mixture of glycosaminoglycans that has been studied for its anti-albuminuric potential. Considering the effects of glycosaminoglycans on endothelial function and sodium homeostasis, we hypothesized that sulodexide may lower blood pressure (BP). In this meta-analysis, we therefore investigated the antihypertensive effects of sulodexide treatment.
METHODS: We selected randomized controlled trials that investigated sulodexide treatment of at least 4 weeks and measured BP at baseline and after treatment. Two reviewers independently extracted data on study design, risk of bias, population characteristics and outcome measures. In addition, we contacted authors and pharmaceutical companies to provide missing data.
RESULTS: Eight studies, totalling 3,019 subjects (mean follow-up: 4.4 months) were included. Mean age was 61 years and mean baseline BP was 135/75 mmHg. Compared to control treatment, sulodexide resulted in a significant systolic (2.2 mmHg [95% CI 0.3-4.1], p = 0.02) and diastolic BP reduction (1.7 mmHg [0.6-2.9], p = 0.004). Hypertensive patients displayed the largest systolic BP and diastolic BP reductions (10.2/5.4 mmHg, p < 0.001). Higher baseline systolic and diastolic BP were significantly associated with larger systolic (R(2)  = 0.83, p < 0.001) and diastolic BP (R(2)  = 0.41, p = 0.02) reductions after sulodexide treatment. In addition, systolic (R(2)  = 0.41, p = 0.03) and diastolic BP reductions (R(2)  = 0.60, p = 0.005) were significantly associated with albuminuria reduction.
CONCLUSION: Our data suggest that sulodexide treatment results in a significant BP reduction-especially in hypertensive subjects. This indicates that endothelial glycosaminoglycans might be an independent therapy target in cardiovascular disease. Future studies should further address the BP lowering potential of sulodexide.

PMID: 26184982 [PubMed – as supplied by publisher]

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The renal protective effect of Angiotensin Receptor Blockers depends on intra-individual response variation in multiple risk markers.

The renal protective effect of Angiotensin Receptor Blockers depends on intra-individual response variation in multiple risk markers.

Br J Clin Pharmacol. 2015 Apr 14;

Authors: Schievink B, de Zeeuw D, Parving HH, Rossing P, Lambers Heerspink HJ

Abstract
AIMS: Angiotensin Receptor Blockers (ARBs) are renoprotective and targeted to blood pressure. However, ARBs have multiple other (off-target) effects which may affect renal outcome. It is unknown whether on-target and off-target effects are congruent within individuals. If not, this variation in short-term effects may have important implications for the prediction of individual long-term renal outcomes. Our aim was to assess intra-individual variability in multiple parameters in response to ARBs in type 2 diabetes.
METHODS: Change in systolic blood pressure (SBP), albuminuria, potassium, hemoglobin, cholesterol and uric acid after 6 months of losartan treatment were assessed in the RENAAL database. Improvement in predictive performance of renal outcomes (ESRD or doubling serum creatinine) for each individual using ARB-induced changes in all risk markers was assessed by relative integrative discrimination index (RIDI).
RESULTS: SBP response showed high variability (mean -5.7 mmHg; 5(th) to 95(th) percentile -36.5 to +24.0 mmHg) between individuals. Changes in off-target parameters also showed high variability between individuals. No congruency was observed between responses to losartan in multiple parameters within individuals. Using individual responses in all risk markers significantly improved renal risk prediction (RIDI 30.4%;p < 0.01) compared to using only SBP changes. Results were successfully replicated in two independent trials with irbesartan; IDNT and IRMA-2.
CONCLUSIONS: In this post-hoc analysis we showed that ARBs have multiple off-target effects which vary between and within individuals. Combining all ARB-induced responses beyond SBP provides a more accurate prediction of who will benefit from ARB therapy. Prospective trials are required to validate these findings.

PMID: 25872610 [PubMed – as supplied by publisher]

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Understanding drug preferences, different perspectives.

Understanding drug preferences, different perspectives.
Br J Clin Pharmacol. 2014 Dec 3;
Authors: Mol PG, Arnardottir AH, Straus SM, de Graeff PA, Haaijer-Ruskamp FM, Quik EH, Krabbe PF, Denig P
Abstract
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Novel drugs and intervention strategies for the treatment of chronic kidney disease.

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Novel drugs and intervention strategies for the treatment of chronic kidney disease.
Br J Clin Pharmacol. 2013 Oct;76(4):536-50
Authors: Lambers Heerspink HJ, de Zeeuw D
Abstract
Chro… Continue reading

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Is combined use of SSRIs and NSAIDs associated with an increased risk of starting peptic ulcer treatment?

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Is combined use of SSRIs and NSAIDs associated with an increased risk of starting peptic ulcer treatment?
Br J Clin Pharmacol. 2013 Dec 2;
Authors: Pouwels KB, Kalkman GA, Schagen D, Visser ST, Hak E
P… Continue reading

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A European approach to categorizing medicines for fitness to drive: outcomes of the DRUID project.

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A European approach to categorizing medicines for fitness to drive: outcomes of the DRUID project.

Br J Clin Pharmacol. 2012 Dec;74(6):920-31

Authors: …

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Medication review and reconciliation with cooperation between pharmacist and general practitioner and the benefit for the patient: a systematic review.

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Medication review and reconciliation with cooperation between pharmacist and general practitioner and the benefit for the patient: a systematic review.

Br J Clin…

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Disturbed development of the enteric nervous system after in utero exposure of selective serotonin re-uptake inhibitors and tricyclic antidepressants. Part 2: Testing the hypotheses.

Disturbed development of the enteric nervous system after in utero exposure of selective serotonin re-uptake inhibitors and tricyclic antidepressants. Part 2: Testing the hypotheses.

Br J…

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Disturbed development of the enteric nervous system after in utero exposure of selective serotonin re-uptake inhibitors and tricyclic antidepressants. Part 1: Literature review.

Disturbed development of the enteric nervous system after in utero exposure of selective serotonin re-uptake inhibitors and tricyclic antidepressants. Part 1: Literature review.

Br J Clin…

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Additional safety risk to exceptionally approved drugs in Europe?

Additional safety risk to exceptionally approved drugs in Europe?

Br J Clin Pharmacol. 2011 Sep;72(3):490-9

Authors: Arnardottir AH, Haaijer-Ruskamp FM, Straus SM, Eichler HG, de…

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Road traffic accidents and psychotropic medication use in The Netherlands: a case-control study.

Road traffic accidents and psychotropic medication use in The Netherlands: a case-control study.

Br J Clin Pharmacol. 2011 Sep;72(3):505-13

Authors: Ravera S, van Rein N, de Gier…

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Methods in pharmacology: measurement of cardiac output.

Methods in pharmacology: measurement of cardiac output.
Br J Clin Pharmacol. 2011 Mar;71(3):316-30
Authors: Geerts BF, Aarts LP, Jansen JR
Abstract
Many methods of cardiac output measurement have been developed… Continue reading

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