OBJECTIVES: Due to the high interindividual variability in vancomycin pharmacokinetics, optimisation of its dosing is still challenging. This study aimed to explore vancomycin pharmacokinetics in adult patients and to propose an easy applicable dosing nomogram for initial treatment. METHODS: Vancomycin pharmacokinetics was calculated in a two-compartmental model based on therapeutic drug monitoring data. A linear regression model was used to explore the relationship between vancomycin elimination half-life and glomerular filtration rate estimated according the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. RESULTS: In the whole study population (n=66), vancomycin volume of distribution, clearance and half-life median (IQR) values were 0.69 (0.58-0.87) L/kg, 0.031 (0.022-0.050) L/h/kg and 14.4 (9.5-25.2) hours, respectively. Vancomycin half-life was associated with glomerular filtration rate (r2=0.4126, p<0.0001) according to the formula: t1/2 (h) = -0.247×eGFRCKD-EPI (mL/min/1.73 m2)+32.89. This relationship was used to construct a dosing nomogram. CONCLUSIONS: We propose an easy-to-use dosing nomogram for vancomycin therapy initiation that allows individualisation of the dosing interval with respect to the administered dose size and functional renal status.

• Klíčová slova
• CKD-EPI, dosing nomogram, glomerular filtration, pharmacokinetics, therapeutic drug monitoring, vancomycin,
• MeSH
• antibakteriální látky * MeSH
• dospělí MeSH
• hodnoty glomerulární filtrace MeSH
• ledviny fyziologie   MeSH
• lidé MeSH
• monitorování léčiv MeSH
• vankomycin * MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky * MeSH
• vankomycin * MeSH

Correct drug dosing of anticancer agents is essential to obtain optimal outcomes. Overdosing will result in increased toxicity, treatment interruption and possible cessation of anticancer treatment. Underdosing may result in suboptimal anti-cancer effects and may increase the risk of cancer-related mortality. As it is practical nor feasible to perform therapeutic drug monitoring for all anti-cancer drugs, kidney function is used to guide drug dosing for those drugs whose primary mode of excretion is through the kidney. However, it is not well-established what method should be utilized to measure or estimate kidney function and the choice of method does influence treatment decisions regarding eligibility for anti-cancer drugs and their dose. In this review, we will provide an overview regarding the importance of drug dosing, the preferred method to determine kidney function and a practical approach to drug dosing of anticancer drugs.

• Klíčová slova
• Chemotherapy, Chronic kidney dysfunction, Drug dosing, Glomerular filtration rate, Outcome, Renal toxicity,
• MeSH
• ledviny účinky léků   MeSH
• lidé MeSH
• monitorování léčiv MeSH
• nádory farmakoterapie   MeSH
• protinádorové látky aplikace a dávkování   MeSH
• výpočet dávky léku * MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• protinádorové látky MeSH

Phenobarbital is a first-line treatment of various seizure types in newborns. Dosage individualization maximizing the proportion of patients with drug levels in therapeutic range or sufficient treatment response is still challenging. The aim of this review was to summarize the available evidence on phenobarbital pharmacokinetics in neonates and to identify its possible covariates suitable for individualization of initial drug dosing. Several covariates have been considered: body weight and height, body surface area, gestational and postnatal age, laboratory parameters of renal and hepatic functions, asphyxia, therapeutic hypothermia, extracorporeal membrane oxygenation (ECMO), drug interactions, and genetic polymorphisms. The most frequently studied and well-founded covariate for the estimation of phenobarbital dosing is actual body weight. Loading dose of 15-20 mg/kg followed by a maintenance dose of 3-5 mg/kg/day seems to be accurate. However, the evidence for the other covariates with respect to dosing individualization is not sufficient. Doses at the lower limit of suggested range should be preferred in patients with severe asphyxia, while the upper limit of the range should be targeted in neonates receiving ECMO support.

• Klíčová slova
• asphyxia, dosing, neonates, pharmacokinetics, phenobarbital,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

This study aimed to explore vancomycin pharmacokinetics and its covariates in critically ill neonates and to propose an easy applicable dosing nomogram for initial treatment. Individual vancomycin pharmacokinetic parameters were calculated based on therapeutic drug monitoring data using a one-compartmental model. A linear regression model was used for examination of covariates. The mean (SD) volume of distribution (Vd) and clearance (CL) for vancomycin were 0.73 (0.31) L/kg and 0.052 (0.020) L/h/kg, respectively. Vd was related to actual body weight (ABW), gestational and postmenstrual age. CL was also associated with ABW, gestational, postmenstrual age and also creatinine clearance. ABW was the strongest predictor for vancomycin pharmacokinetics and consequently dosing. Loading dose (mg) of 11.81 × ABW (kg) + 7.86 and maintenance dose (mg/day) of 40.92 × ABW (kg) -22.18 most closely approximated pharmacokinetic target. Vancomycin pharmacokinetics was mainly influenced by ABW in neonates and a practical ABW-based dosing algorithm was developed.

• Klíčová slova
• Dosing nomogram, Neonates, Pharmacokinetics, Sepsis, Therapeutic drug monitoring, Vancomycin,
• MeSH
• antibakteriální látky aplikace a dávkování   farmakokinetika   MeSH
• lidé MeSH
• monitorování léčiv MeSH
• nomogramy MeSH
• novorozenec MeSH
• sepse farmakoterapie   MeSH
• tělesná hmotnost MeSH
• vankomycin aplikace a dávkování   farmakokinetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Názvy látek
• antibakteriální látky MeSH
• vankomycin MeSH

OBJECTIVES: Low adherence to treatment with bisphosphonates significantly impedes its effectiveness. The objectives were: (1) to compare adherence to oral weekly and monthly bisphosphonates with emphasis on dosing instructions; and (2) to study associations between adherence and beliefs about the bisphosphonate treatment among women ≥ 55 years. METHODS: A multicenter survey was performed in secondary-care patients with osteoporosis. Osteoporosis Specific Morisky Medication Adherence Scale (OS-MMAS), questions on compliance with five dosing instructions and Beliefs about Medicines Questionnaire (BMQ) Specific were used. RESULTS: As many as 363 questionnaires (response rate 95%) were analyzed. Respondents (mean age 69 years) were treated with weekly bisphosphonates (37%) or monthly ibandronate (63%). Based on OS-MMAS, 67% of respondents showed high adherence with no differences between the subgroups. Only 44% of respondents were compliant with all dosing instructions. Compliance with dosing instructions concerning time interval (fasting and staying upright) was 71% in weekly and 52% in monthly subgroups, respectively (p < 0.001). Compliance with dosing instructions correlated positively with education (p = 0.009). The mean BMQ necessity score of 18.4 was greater than the mean BMQ concerns score of 13.3. OS-MMAS score correlated with necessity (p = 0.010). Persistence derived from OS-MMAS correlated with both necessity (p = 0.014) and concerns (p = 0.041). CONCLUSION: Despite relatively high adherence to the treatment, most patients do not follow dosing instructions. Reduced bioavailability, particularly of monthly ibandronate, can be expected in clinical practice. Adherence-related outcomes are associated with beliefs about the oral treatment with bisphosphonates.

• Klíčová slova
• DOSING INSTRUCTIONS, DOSING INTERVAL, MEDICATION ADHERENCE, NECESSITY-CONCERNS FRAMEWORK, ORAL BISPHOSPHONATES, OSTEOPOROSIS,
• MeSH
• adherence k farmakoterapii psychologie   MeSH
• aplikace orální MeSH
• bisfosfonáty aplikace a dávkování   terapeutické užití   MeSH
• hodnocení adherence k farmakoterapii * MeSH
• inhibitory kostní resorpce aplikace a dávkování   terapeutické užití   MeSH
• kyselina ibandronová MeSH
• lidé středního věku MeSH
• lidé MeSH
• postmenopauzální osteoporóza farmakoterapie   psychologie   MeSH
• průřezové studie MeSH
• průzkumy a dotazníky MeSH
• průzkumy zdravotní péče MeSH
• rozvrh dávkování léků MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• zdraví - znalosti, postoje, praxe * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• bisfosfonáty MeSH
• inhibitory kostní resorpce MeSH
• kyselina ibandronová MeSH

BACKGROUND: The dosing of aminoglycosides (AGs) in patients with kidney disease is challenging due to their markedly prolonged half-life, which renders pulse dosing schedules unsuitable. We performed a review of the literature that describes the pharmacokinetics of, and dosing recommendations for, AG for patients with abnormal renal functions and various renal replacement therapy modalities, focusing on patients treated with intermittent hemodialysis (iHD). SUMMARY: During one iHD session, dialysis removes a remarkable amount of the drug regardless of the dialyzer type. In patients with severely reduced kidney functions, the distribution phase is prolonged, which needs to be taken into account when drawing samples shortly after drug administration or following an iHD session. KEY MESSAGES: The doses recommended for the pulse dosing of patients without kidney disease leads to unacceptably high overall systemic exposure for patients with severely reduced kidney functions even with dosing intervals extended up to 48 h. Therefore, lower doses accompanied by extended dosing intervals must be applied for this patient group. The clinical evidence and current recommendations support the dosing of AG following, rather than before, HD sessions. In patients with end-stage kidney disease, the samples for TDM of AGs should not be drawn earlier than 2 h after end of the infusion and 4 h after the end of iHD session to allow full (re)distribution of the drug.

• Klíčová slova
• Amikacin, Conventional dosing, Dialysis membranes, Gentamicin, Pulse dosing, Renal dialysis, Renal insufficiency, Tobramycin,
• MeSH
• aminoglykosidy farmakokinetika   terapeutické užití   MeSH
• antibakteriální látky farmakokinetika   terapeutické užití   MeSH
• chronická renální insuficience * komplikace   MeSH
• chronické selhání ledvin * komplikace   MeSH
• dialýza ledvin MeSH
• lidé MeSH
• náhrada funkce ledvin MeSH
• renální insuficience * komplikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• aminoglykosidy MeSH
• antibakteriální látky MeSH

Dabigatran is increasingly being used in clinical practice for the thromboprophylaxis in atrial fibrillation as a convenient therapy that needs no drug level monitoring. However, analysis of the data of the same clinical trial that led to the adoption of dabigatran in fixed-dosing regimens has indicated a small subgroup of patients that could be either over-treated, risking bleeding, or under-treated, risking embolism. Additional post-marketing data lends support to the favorable therapeutic profile of dabigatran but at the same time raises doubts about patient characteristics such as weight, age, renal function and their pharmacokinetic effects that, in some cases, could be serious enough to expose a minority of patients to risk. We will present a clinical case of a patient with an ischemic stroke while on dabigatran that was found with low dabigatran plasma levels and we will discuss the currently available data on the effects of inherent patient characteristics on dabigatran pharmacokinetics, the clinical impact of dabigatran plasma levels on safety and efficacy as well as the possibility of improving the risk-benefit profile of this agent by tailoring the dose for selected patient groups.

• Klíčová slova
• atrial fibrillation, dabigatran, dosing,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Oral budesonide 9 mg/day represents first-line treatment of mild-to-moderately active ileocolonic Crohn's disease. However, there is no precise recommendation for budesonide dosing due to lack of comparative data. A once-daily (OD) 9 mg dose may improve adherence and thereby efficacy. METHODS: An eight-week, double-blind, double-dummy randomised trial compared budesonide 9 mg OD versus 3mg three-times daily (TID) in patients with mild-to-moderately active ileocolonic Crohn's disease. Primary endpoint was clinical remission defined as CDAI <150 at week 8 (last observation carried forward). RESULTS: The final intent-to-treat population comprised 471 patients (238 [9 mg OD], 233 [3 mg TID]). The confirmatory population for the primary endpoint analysis was the interim per protocol population (n=377; 188 [9 mg OD], 189 [3mg TID]), in which the primary endpoint was statistically non-inferior with budesonide 9 mg OD versus 3 mg TID. Clinical remission was achieved in 71.3% versus 75.1%, a difference of -3.9% (95% CI [-14.6%; 6.4%]; p=0.020 for non-inferiority). The mean (SD) time to remission was 21.9 (13.8) days versus 21.4 (14.6) days with budesonide 9 mg OD versus 3 mg TID, respectively. In a subpopulation of 122 patients with baseline SES-CD ulcer score ≥1, complete mucosal healing occurred in 32.8% (21/64) on 9 mg OD and 41.4% (24/58) on 3mg TID; deep remission (mucosal healing and clinical remission) was observed in 26.6% (17/64) and 32.8% (19/58) of patients, respectively. Treatment-emergent suspected adverse drug reactions were reported in 4.6% of 9 mg OD and 4.7% of 3 mg TID patients. CONCLUSIONS: Budesonide at the recommended dose of 9 mg/day can be administered OD without impaired efficacy and safety compared to 3mg TID dosing in mild-to-moderately active Crohn's disease.

• Klíčová slova
• Adherence, Budesonide, Clinical remission, Crohn's disease, Dosing,
• MeSH
• adherence pacienta MeSH
• aplikace orální MeSH
• budesonid aplikace a dávkování   MeSH
• Crohnova nemoc farmakoterapie   patologie   MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• gastrointestinální endoskopie MeSH
• glukokortikoidy aplikace a dávkování   MeSH
• indukce remise MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• následné studie MeSH
• prospektivní studie MeSH
• rozvrh dávkování léků MeSH
• senioři MeSH
• střevní sliznice patologie   MeSH
• výsledek terapie MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• budesonid MeSH
• glukokortikoidy MeSH

Cannabis has been employed medicinally throughout history, but its recent legal prohibition, biochemical complexity and variability, quality control issues, previous dearth of appropriately powered randomised controlled trials, and lack of pertinent education have conspired to leave clinicians in the dark as to how to advise patients pursuing such treatment. With the advent of pharmaceutical cannabis-based medicines (Sativex/nabiximols and Epidiolex), and liberalisation of access in certain nations, this ignorance of cannabis pharmacology and therapeutics has become untenable. In this article, the authors endeavour to present concise data on cannabis pharmacology related to tetrahydrocannabinol (THC), cannabidiol (CBD) et al., methods of administration (smoking, vaporisation, oral), and dosing recommendations. Adverse events of cannabis medicine pertain primarily to THC, whose total daily dose-equivalent should generally be limited to 30mg/day or less, preferably in conjunction with CBD, to avoid psychoactive sequelae and development of tolerance. CBD, in contrast to THC, is less potent, and may require much higher doses for its adjunctive benefits on pain, inflammation, and attenuation of THC-associated anxiety and tachycardia. Dose initiation should commence at modest levels, and titration of any cannabis preparation should be undertaken slowly over a period of as much as two weeks. Suggestions are offered on cannabis-drug interactions, patient monitoring, and standards of care, while special cases for cannabis therapeutics are addressed: epilepsy, cancer palliation and primary treatment, chronic pain, use in the elderly, Parkinson disease, paediatrics, with concomitant opioids, and in relation to driving and hazardous activities.

• Klíčová slova
• Adverse events, Cannabinoids, Cannabis, Drug abuse, Marijuana, Psychopharmacology,
• MeSH
• bolest farmakoterapie   MeSH
• Cannabis * MeSH
• fixní kombinace léků MeSH
• kanabidiol aplikace a dávkování   farmakologie   MeSH
• lidé MeSH
• marihuana pro léčebné účely aplikace a dávkování   farmakologie   MeSH
• rozvrh dávkování léků MeSH
• tetrahydrokanabinol aplikace a dávkování   farmakologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zánět farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• fixní kombinace léků MeSH
• kanabidiol MeSH
• marihuana pro léčebné účely MeSH
• nabiximols MeSH Prohlížeč
• tetrahydrokanabinol MeSH

BACKGROUND: Antibiotic exposure in intensive care patients with sepsis is frequently inadequate and is associated with poorer outcomes. Antibiotic dosing is challenging in the intensive care, as critically ill patients have altered and fluctuating antibiotic pharmacokinetics that make current one-size-fits-all regimens unsatisfactory. Real-time bedside dosing software is not available yet, and therapeutic drug monitoring is typically used for few antibiotic classes and only allows for delayed dosing adaptation. Thus, adequate and timely antibiotic dosing continues to rely largely on the level of pharmacokinetic expertise in the ICU. Therefore, we set out to assess the level of knowledge on antibiotic pharmacokinetics among these intensive care professionals. METHODS: In May 2018, we carried out a cross-sectional study by sending out an online survey on antibiotic dosing to more than 20,000 intensive care professionals. Questions were designed to cover relevant topics in pharmacokinetics related to intensive care antibiotic dosing. The preliminary pass mark was set by members of the examination committee for the European Diploma of Intensive Care using a modified Angoff approach. The final pass mark was corrected for clinical relevance as assessed for each question by international experts on pharmacokinetics. RESULTS: A total of 1448 respondents completed the survey. Most of the respondents were intensivists (927 respondents, 64%) from 97 countries. Nearly all questions were considered clinically relevant by pharmacokinetic experts. The pass mark corrected for clinical relevance was 52.8 out of 93.7 points. Pass rates were 42.5% for intensivists, 36.1% for fellows, 24.8% for residents, and 5.8% for nurses. Scores without correction for clinical relevance were worse, indicating that respondents perform better on more relevant topics. Correct answers and concise clinical background are provided. CONCLUSIONS: Clinically relevant pharmacokinetic knowledge on antibiotic dosing among intensive care professionals is insufficient. This should be addressed given the importance of adequate antibiotic exposure in critically ill patients with sepsis. Solutions include improved education, intensified pharmacy support, therapeutic drug monitoring, or the use of real-time bedside dosing software. Questions may provide useful for teaching purposes.

• Klíčová slova
• Antibiotics, Drug dosing, Intensive care, Pharmacokinetics,
• MeSH
• antibakteriální látky aplikace a dávkování   farmakokinetika   terapeutické užití   MeSH
• dospělí MeSH
• jednotky intenzivní péče organizace a řízení   statistika a číselné údaje   MeSH
• klinické kompetence normy   statistika a číselné údaje   MeSH
• kritický stav terapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monitorování léčiv metody   MeSH
• průřezové studie MeSH
• průzkumy a dotazníky MeSH
• sepse farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH