Nederlands Platform voor Farmaceutisch Onderzoek

Het Nederlands Platform voor Farmaceutisch Onderzoek (NPFO) presenteert onderzoek in de farmaceutische wetenschappen, zoals medicatieveiligheid, patiëntenzorg, formulering, (bio)analyse, (klinische) farmacologie en casuïstiek.

Vroeg ingrijpen met RAAS-remmers bij diabeten vertraagt achteruitgang nierfunctie

Marcel Kooij

Rubriek: Referaat
Identificatie: 2016;1:e1605
Datum: 8 februari 2016

Intoxicatie met een cocktail van drie antihypertensiva

J.B. Masselink*, E.T. Sportel en H.B.B. Colen

Lees abstract

Intoxication after ingestion of three different antihypertensive drugs

INTRODUCTION

The use of multiple drugs to treat hypertension is very common. Monointoxications with beta-blockers or calcium antagonists are often seen. Multiple drug intoxications with co-ingestion of angiotensin receptor blockers are a rarity.

DESCRIPTION

A 46-year-old male was admitted to our hospital with a suspected intoxication of beta-blockers and calcium channel blockers. Toxicological screening in serum showed that, in addition to toxic amounts of metoprolol and amlodipine, the patient also ingested a large amount of the angiotensin receptor blocker valsartan. The patient developed severe refractory shock, kidney and liver failure. Little is known about the treatment of an intoxication with angiotensin receptor blockers. Treatment focused on organ failure, which included the intravenous administration of inotropic medication, insulin, glucagon and calcium gluconate.

DISCUSSION

The clinical course may be explained by the patient’s blood levels of the ingested drugs. At day 1 and 2, all measured concentrations were found to be in the toxic range. At this point both shock and kidney and liver failure were present. At day 5 the concentration metoprolol was in the therapeutic range, while amlodipine and valsartan were still toxic. However, the patient was declared hemodynamically stable, but organ failure was still present. It is known that amlodipine and valsartan can cause kidney failure, but liver failure without heart failure is not seen with amlodipine. This may indicate that liver failure is caused by valsartan.

CONCLUSION

A multiple drug intoxication with various antihypertensive agents can be severe. Different organs can be harmed and need support with inotropic medications and antidotes. It is possible that valsartan can cause liver failure when an overdose is ingested.

Rubriek: Casuïstische mededeling
Identificatie: 2016;1:a1607
Datum: 2 februari 2016

Dried blood spots voor het bepalen van de serumconcentratie van tamoxifen en zijn actieve metaboliet endoxifen

Nynke G.L. Jager a*, Hilde Rosing a, Jan H.M. Schellens bc, Jos H. Beijnen abc en Sabine C. Linn de

Lees abstract

Use of dried blood spots for the determination of serum concentrations of tamoxifen and endoxifen

OBJECTIVE

To establish the relationship between dried blood spot (DBS) and serum concentrations of tamoxifen and endoxifen in order to allow the use of DBS sampling, a simple and patient-friendly alternative to venous sampling, in clinical practice. The anti-estrogenic effect of tamoxifen is suggested to be mainly attributable to its metabolite endoxifen, and a minimum therapeutic threshold for endoxifen in serum has been proposed.

DESIGN AND METHODS

Paired DBS and serum samples were obtained from 50 patients using tamoxifen and analysed using HPLC-MS/MS. Serum concentrations were calculated from DBS concentrations using the formula: calculated serum concentration = DBS concentration/[(1 – haematocrit) + (blood cell/serum ratio) × haematocrit]. The blood cell/serum ratio was determined ex vivo by incubating a batch of whole blood spiked with both analytes and imputed as a fixed value. The average haematocrit for female adults was imputed as a fixed value. Calculated and analysed serum concentrations were compared using weighted Deming regression.

RESULTS

Weighted Deming regression analysis comparing 44 matching pairs of DBS and serum samples showed a proportional bias for both analytes. Serum concentrations were calculated using [Tam]s,calc = [Tam]DBS/0.779 and [End]s,calc = [End]DBS/0.663. Calculated serum concentrations were within 20% of analysed serum concentrations in 84 and 100% of patient samples for tamoxifen and endoxifen, respectively.

CONCLUSION

DBS concentrations of tamoxifen and endoxifen were equal to serum concentrations after correction for haematocrit and blood cell/serum ratio. DBS sampling can be used in clinical practice.

Rubriek: Oorspronkelijk artikel
Identificatie: 2016;1:a1605
Datum: 1 februari 2016

Waarmee rekening houden bij de productie van oromucosale film?

András Vermes

Rubriek: Referaat
Identificatie: 2016;1:e1608
Datum: 26 januari 2016

Apotheekinterventies bij postoperatieve patiënten

András Vermes

Rubriek: Referaat
Identificatie: 2016;1:e1607
Datum: 25 januari 2016

Model voor kosteneffectiviteit en klinische uitkomsten

Rogier Klok

Rubriek: Referaat
Identificatie: 2016;1:e1604
Datum: 22 januari 2016

Kwaliteitsindicatoren voor antibioticagebruik in ziekenhuizen

Rogier Klok

Rubriek: Referaat
Identificatie: 2016;1:e1603
Datum: 21 januari 2016

Vergelijking van opvolgingspercentages bij twee communicatiemethoden en invloed van adviesfunctionaris bij de presentatie van adviezen uit een klinisch beslissingsondersteunend systeem op een afdeling geriatrie

K.M. Barmentlo-Andringa a*, A.T.M. Wasylewicz b, J.M.G.A. Schols c, R.J.E. Grouls b en C.M.J. van der Linden a

Lees abstract

Comparing compliance of two communication methods of CDSS-generated advices communicated by professionals with different background qualifications on a geriatric ward

OBJECTIVE

To determine whether two active alert communication methods – telephone intervention or live intervention – and communication by differently qualified persons, lead to differences in alert compliance on a geriatric ward.

DESIGN

Prospective intervention study.

METHODS

All patients admitted to the geriatric department of a Dutch hospital were included. The clinical decision support system (CDSS), Gaston, generated alerts using eighteen clinical rules. Relevant alerts were communicated with prescribers using two communication methods: telephone intervention, where the alerts were communicated by the hospital pharmacist by telephone, and live intervention, where the alerts were communicated by a medical research student on the ward. If the correct action occurred after alert communication, this was scored as alert compliance. A review session was used to evaluate the correctness of the alert classification during the study.

RESULTS

The CDSS generated 148 unique alerts during both study periods. Alert compliance was 29% (n = 17/58) for telephone intervention and 31% (n = 27/90) for live intervention. Expressed as percentage of relevant alerts, telephone intervention (61%, n = 14/28) resulted in better alert compliance than live intervention (44%, n = 27/62, P = 0.131). The review session showed that of 20 reviewed alerts 8 (40%) were classified differently compared with the initial alert classification for both alert methods.

CONCLUSION

This study showed no preference for either telephone intervention or live intervention as the better alert communication method. The results demonstrate that profession and knowledge of the person who judged the alerts affects the quality of alert classification.

Rubriek: Oorspronkelijk artikel
Identificatie: 2016;1:a1604
Datum: 20 januari 2016

Afgiftemechanisme van tobramycine, colistine en nystatine uit mondpasta voor selectieve decontaminatie van de mondholte

S. Akbarali a*, R.W. Kalicharan ab en H. Vromans ab

Lees abstract

Mechanism of release of tobramycin, colistin and nystatin from a mouth paste applied to selectively decontaminate the oral cavity

OBJECTIVE

To study the in vitro release of the compounds tobramycin sulphate (TS), colistin sulphate (CS) and nystatin from the oral paste for selective oropharyngeal decontamination.

DESIGN AND METHODS

The release of the active compounds was studied for 2 hours in a medium of phosphate buffer using various methods. Diffusion was studied with the paddle apparatus. Sedimentation was examined by spreading the paste on a filter paper and exposing this to the medium so that the particles could settle. The chewing motion was mimicked with a disintegration apparatus. Finally, the influence of 10, 20, 30 and 40% hydroxypropylmethylcellulose (HPMC) concentrations on drug release was studied.

RESULTS

With the diffusion test the highest release was seen with TS (5.7%) and the lowest with nystatin (0.3%). With sedimentation the release of all three compounds was at least twice as high as with diffusion (TS: 14.0% vs 5.7%; CS: 6.3% vs 2.7%; nystatin: 0.9% vs 0.3%). Chewing motions influenced the release too (TS: 44.6%; CS: 16.4%; nystatin: 2.1%): the release was 2.5-3 times higher than with sedimentation. Increasing the HPMC concentration in the mouth paste improved the release of TS and CS, though it had little effect on nystatin (40% HPMC resulted in release of TS: 70.9%; CS: 37.5%; nystatin: 0.8%).

CONCLUSION

Drug release from the mouth paste by diffusion is incomplete. Chewing motions and increasing HPMC concentrations (along with sedimentation) enhance the release of the active compounds. To improve release of TS and CS, more HPMC should be used in the formulation.

Rubriek: Korte bijdrage
Identificatie: 2016;1:a1602
Datum: 19 januari 2016

Praktijkonderzoek naar effect van depressie op therapietrouw

Jacqueline Hugtenburg

Rubriek: Referaat
Identificatie: 2016;1:e1602
Datum: 18 januari 2016

Dankbetuiging

Rubriek: Redactionele mededeling
Identificatie: 2016;1:e1601
Datum: 18 januari 2016

Speeksel als matrix voor meting van pyrazinamide bij farmacokinetisch onderzoek en therapeutic drug monitoring

C.A.W. Heijens a*, H.H. Semvua b, C.M. Mtabho b, M.J. Teulen c, A.P. Colbers c, P.M.G. Filius a, D.M. Burger c, G.S. Kibiki b en R.E. Aarnoutse c

Lees abstract

Saliva as a matrix for the measurement of pyrazinamide in pharmacokinetic studies or therapeutic drug monitoring

OBJECTIVE

To describe the pharmacokinetics of pyrazinamide in saliva and to assess whether saliva can be a matrix for pharmacokinetic studies and therapeutic drug monitoring (TDM).

DESIGN AND METHODS

Intensive pharmacokinetic sampling for both plasma and saliva took place during 24 h in 15 adult tuberculosis patients in Moshi, Tanzania. Pharmacokinetic parameters for both matrices were derived from the measured saliva and total (protein-bound plus unbound) plasma concentrations of pyrazinamide. The reciprocal saliva/plasma concentration ratio was used to estimate plasma concentrations based on the measured salivary concentrations. The predictive performance of these estimations was assessed by the jackknife method.

RESULTS

Geometric means of AUC0-24 and Cmax of pyrazinamide in saliva were 61% and 78%, respectively, of the corresponding values in plasma. tmax in saliva was similar to that in plasma. Salivary concentrations and total plasma concentrations (n = 133) were strongly correlated (Spearman’s rho = 0.909; P < 0.001). The mean plasma/saliva concentration ratio was 0.637 (CI95 0.600-0.673). The ratio was dependent on the sampling time. It was highest in the absorption phase and decreased afterwards. Bias and imprecision of the prediction of total pyrazinamide plasma concentrations based on salivary concentrations were 5.5% and 24.7%, respectively. Using samples in a time window of t = 2-8 h post dose, bias was 13.5% and imprecision was 21.4%.

CONCLUSION

The exposure to pyrazinamide in saliva is relatively high, but less than the exposure in plasma. The saliva/plasma concentration ratio was time-dependent, contributing to an insufficient predictive performance (imprecision > 20%). Based on this study saliva measurements of pyrazinamide can only be used for a semiquantitative assessment of pyrazinamide plasma concentrations.

Rubriek: Korte bijdrage
Identificatie: 2016;1:a1601
Datum: 18 januari 2016

Contact

Redacteur / secretaris
Arjan Polderman

(070) 373 73 14 npfo@npfo.nl