			Home About us Contact

Dose Ratio (dose + ratio)

Distribution by Scientific Domains

Medical Sciences	81%
Life Sciences	18%

Selected Abstracts

Estimation of endogenous adenosine activity at adenosine receptors in guinea-pig ileum using a new pharmacological method

ACTA PHYSIOLOGICA, Issue 2 2010
K. F. Nilsson
Abstract Aim:, Adenosine modulates neurotransmission and in the intestine adenosine is continuously released both from nerves and from smooth muscle. The main effect is modulation of contractile activity by inhibition of neurotransmitter release and by direct smooth muscle relaxation. Estimation of adenosine concentration at the receptors is difficult due to metabolic inactivation. We hypothesized that endogenous adenosine concentrations can be calculated by using adenosine receptor antagonist and agonist and dose ratio (DR) equations. Methods:, Plexus-containing guinea-pig ileum longitudinal smooth muscle preparations were made to contract intermittently by electrical field stimulation in organ baths. Schild plot regressions were constructed with 2-chloroadenosine (agonist) and 8-(p -sulfophenyl)theophylline (8-PST; antagonist). In separate experiments the reversing or enhancing effect of 8-PST and the inhibiting effect of 2-chloroadenosine (CADO) were analysed in the absence or presence of an adenosine uptake inhibitor (dilazep), and nucleoside overflow was measured by HPLC. Results:, Using the obtained DR, baseline adenosine concentration was calculated to 28 nm expressed as CADO activity, which increased dose dependently after addition of 10,6 m dilazep to 150 nm (P < 0.05). HPLC measurements yielded a lower fractional increment (80%) in adenosine during dilazep, than found in the pharmacological determination (440%). Conclusion:, Endogenous adenosine is an important modulator of intestinal neuro-effector activity, operating in the linear part of the dose,response curve. Other adenosine-like agonists might contribute to neuromodulation and the derived formulas can be used to calculate endogenous agonist activity, which is markedly affected by nucleoside uptake inhibition. The method described should be suitable for other endogenous signalling molecules in many biological systems. [source]

Significance testing of synergistic/antagonistic, dose level-dependent, or dose ratio-dependent effects in mixture dose-response analysis

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 10 2005
Martijs J. Jonker
Abstract In ecotoxicology, the state of the art for effect assessment of chemical mixtures is through multiple dose,response analysis of single compounds and their combinations. Investigating whether such data deviate from the reference models of concentration addition and/or independent action to identify overall synergism or antagonism is becoming routine. However, recent data show that more complex deviation patterns, such as dose ratio,dependent deviation and dose level,dependent deviation, need to be addressed. For concentration addition, methods to detect such deviation patterns exist, but they are stand-alone methods developed separately in literature, and conclusions derived from these analyses are therefore difficult to compare. For independent action, hardly any methods to detect such deviations from this reference model exist. This paper describes how these well-established mixture toxicity principles have been incorporated in a coherent data analysis procedure enabling detection and quantification of dose level,and dose ratio,specific synergism or antagonism from both the concentration addition and the independent action models. Significance testing of which deviation pattern describes the data best is carried out through maximum likelihood analysis. This analysis procedure is demonstrated through various data sets, and its applicability and limitations in mixture research are discussed. [source]

The role of methadone in cancer pain treatment , a review

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 7 2009
W. Leppert
Summary Background:, Methadone is an opioid analgesic of step 3 of the World Health Organization (WHO) analgesic ladder. Aim and Methods:, To outline pharmacodynamics, pharmacokinetics, drug interactions, equianalgesic dose ratio with other opioids, dosing rules, adverse effects and methadone clinical studies in patients with cancer pain. A review of relevant literature on methadone use in cancer pain was conducted. Results:, Methadone is used in opioid rotation and administered to patients with cancer pain not responsive to morphine or other strong opioids when intractable opioid adverse effects appear. Methadone is considered as the first strong opioid analgesic and in patients with renal impairment. Methadone possesses different pharmacodynamics and pharmacokinetics in comparison to other opioids. The advantages of methadone include multimode analgesic activity, high oral and rectal bioavailability, long lasting analgesia, lack of active metabolites, excretion mainly with faeces, low cost and a weak immunosuppressive effect. The disadvantages include long and changeable plasma half-life, high bound to serum proteins, metabolism through P450 system, numerous drug interactions, lack of clear equianalgesic dose ratio to other opioids, QT interval prolongation, local reactions when administered subcutaneously. Conclusions:, Methadone is an important opioid analgesic at step 3 of the WHO analgesic ladder. Future controlled studies may focus on establishment of methadone equianalgesic dose ratio with other opioids and its role as the first strong opioid in comparative studies with analgesia, adverse effects and quality of life taken into consideration. [source]

Sedation with ketamine and low-dose midazolam for short-term procedures requiring pharyngeal manipulation in young children

PEDIATRIC ANESTHESIA, Issue 1 2008
HELENA NOVAK MD
Summary Background:, Pediatric intestinal biopsy procedures including considerable transpharyngeal manipulation of a wire-guided metal capsule require adequate sedation or anesthesia. This retrospective cohort study was designed to evaluate intravenous sedation with ketamine and low-dose midazolam in young children undergoing these procedures before and also after discharge from the hospital. Methods:, A total of 244 biopsy procedures in 217 children under the age of 16 years were evaluated. All anesthesia records were reviewed according to a defined study protocol and in 145 cases the parents were also interviewed by telephone to obtain further information on possible adverse effects before and after discharge. Results:, Ketamine and low-dose midazolam were carefully titrated by an experienced anesthesia team at an approximate dose ratio of 40 : 1 (total doses 2.3 and 0.05 mg·kg,1) in continuously monitored spontaneously breathing children. Possibly associated problems before discharge were salivation (5.7%), vomiting (4.9%), oxygen desaturation (3.3%), laryngospasm (2.5%) and rash (1.2%) according to the patient records and blurred vision (27%), nausea and vomiting (19%), vertigo (13%) and hallucinations or nightmares (3.5%) according to telephone interviews. Few, mild and transient problems remained after discharge from the hospital. Conclusions:, Careful titration of ketamine and low-dose midazolam provides adequate sedation for nonsurgical pediatric short-term procedures also requiring considerable pharyngeal manipulation, particularly considering the low number of serious airway problems such as laryngospasm. The high incidence of late postoperative problems suggests that prospective studies should be designed for long-term follow-up of young children subjected to sedation or anesthesia. [source]

Opioid switching from transdermal fentanyl to oral methadone in patients with cancer pain

CANCER, Issue 12 2004
Miguel Angel Benítez-Rosario M.D., Ph.D.
Abstract BACKGROUND Patients with cancer often are rotated from other opioids to methadone to improve the balance between analgesia and side effects. To the authors' knowledge, no clear guidelines currently exist for the safe and effective rotation from transdermal fentanyl to methadone. METHODS The authors evaluated a protocol for switching opioid from transdermal fentanyl to oral methadone in 17 patients with cancer. Reasons for switching were uncontrolled pain (41.1% of patients) and neurotoxic side effects (58.9% of patients). Methadone was initiated 8,24 hours after fentanyl withdrawal, depending on the patient's previous opioid doses (from < 100 ,g per hour to > 300 ,g per hour). The starting methadone dose was calculated according to a 2-step conversion between transdermal fentanyl:oral morphine (1:100 ratio) and oral morphine:oral methadone (5:1 ratio or 10:1 ratio). The correlation between previous fentanyl dose and the final methadone dose or the fentanyl:methadone dose ratio was assessed by means of Pearson and Spearman correlation coefficients (r), respectively. A Friedman test was used to compare pain intensity before and after the switch and the use of daily rescue doses. RESULTS Opioid rotation was fully or partially effective in 80% and 20%, respectively, of patients with somatic pain. Neuropathic pain was not affected by opioid switching. Delirium and myoclonus were reverted in 80% and 100% of patients, respectively, after opioid switching. A positive linear correlation was obtained between the fentanyl and methadone doses (Pearson r, 0.851). Previous fentanyl doses were not correlated with the final fentanyl:methadone dose ratios (Spearman r, , 0.327). CONCLUSIONS The protocol studied provided a safe approach for switching from transdermal fentanyl to oral methadone, improving the balance between analgesia and side effects in patients with cancer. Cancer 2004. © 2004 American Cancer Society. [source]

The bronchial response to mannitol is attenuated by a previous methacholine test: but not vice versa

CLINICAL & EXPERIMENTAL ALLERGY, Issue 7 2009
E. Gade
Summary Aim To examine the airway response to inhaled mannitol performed before or after a methacholine challenge test in a group of asthmatics with different levels of disease. Methods A total of 48 asthmatics, 18,73 years of age, were included in the study. Two pairs of challenges were performed in a random order on two separate days 24 h apart: either with mannitol performed first on day one, followed 1 h by methacholine, and methacholine as the first on day two, followed 1 h by mannitol or vice versa. A questionnaire-based interview was performed and lung function, exhaled nitric oxide, skin prick test, and blood eosinophil count were measured. Results A total of 44% of the asthmatics used inhaled corticosteroids and 48% were atopic. The airway response to mannitol was attenuated when mannitol was given after methacholine, compared with the response to mannitol when it was given first [log response dose ratio (RDR): 1.42 vs. 1.60 (P=0.004)], whereas the response to methacholine was unchanged in the opposite test order [log RDR: 0.81 vs. 0.96 (P=0.102)]. Conclusion Bronchial challenges with inhaled mannitol and methacholine may be performed on the same day but provocation with mannitol should be performed before methacholine. [source]

Current Evidence on the Unit Equivalence of Different Botulinum Neurotoxin A Formulations and Recommendations for Clinical Practice in Dermatology

DERMATOLOGIC SURGERY, Issue 1 2009
SYRUS KARSAI MD
BACKGROUND The unit equivalence between the two main Botulinum neurotoxin A (BoNTA) preparations, Dysport (Ipsen Ltd., Slough, Berkshire, UK) and BOTOX (Allergan Inc., Irvine, CA), is a matter of discussion. The UK assay used to test Dysport is more sensitive than the U.S. assay used for BOTOX, resulting in a different efficacy per unit in both formulations. Ratios ranging from 6:1 to 1:1 can be found in the literature, but the more recently published literature suggests that 1 unit of BOTOX is equivalent to approximately 2 to 4 units of Dysport (ratio 2:1,4:1). OBJECTIVE Because the number of BoNTA treatments is constantly increasing, these differences warrant a systematic review of published evidence about the unit equivalence of UK and U.S. formulations. METHODS The review is based on a detailed literature research in all relevant databases (MEDLINE, PubMed, Cochrane Library, specialist textbooks). RESULTS The present review supports the recent assumption that dose ratios of less than 3:1 (e.g., 2.5:1 or even 2:1) between Dysport and BOTOX are probably more suitable. CONCLUSIONS The current evidence is still insufficient, and further investigation of lower dose ratios is recommended. [source]

Interindividual variation of serum haloperidol concentrations in Japanese patients , clinical considerations on steady-state serum level,dose ratios

JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 2 2003
E. Yukawa
Summary Objective:, Marked interpatient variability in haloperidol (HAL) level,dose (L/D) ratios makes it difficult to use the administered dose for predicting serum concentrations. Objective:, To investigate the effect of dose, age, total body weight and co-medication on steady-state HAL L/D ratios. Method:, Retrospective analysis of dose and HAL blood level data from 168 patients. Results:, The HAL L/D ratio decreased curvilinearly with increasing daily dose of HAL. The patients treated with concomitant antiparkinsonian drugs showed a mean HAL L/D ratio that was 24·9% higher than those without antiparkinsonian drugs. The patients treated with concomitant antiepileptic drugs showed a mean HAL L/D ratio that was 27·2% lower than those without antiepileptic drugs. The mean HAL L/D ratio of patients treated with concomitant CYP2D6 substrates was not significantly different from those without CYP2D6 substrates. Conclusion:, There is a wide interindividual variability in blood levels of HAL in patients given the same dose. Routine monitoring of HAL serum level is useful, especially in patients who require associated antiepileptic and/or antiparkinsonian medication. [source]

Population pharmacokinetic modelling of aripiprazole and its active metabolite, dehydroaripiprazole, in psychiatric patients

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 6 2008
Jung-Ryul Kim
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT , Almost all reported studies have investigated the pharmacokinetics of aripiprazole in healthy volunteers. , The pharmacokinetics of dehydroaripiprazole have not been identified in a combined model with aripiprazole. WHAT THIS STUDY ADDS , The data on aripiprazole and dehydroaripiprazole in psychiatric patients were modelled jointly using a population approach. , The apparent clearance of aripiprazole in cytochrome P450 (CYP) 2D6 intermediate metabolizers (IM) was approximately 60% of that in CYP2D6 extensive metabolizers (EM) having two functional alleles, but the exposure to dehydroaripiprazole in CYP2D6 IM was similar to that in EM. AIMS The aims of this study were to develop a combined population pharmacokinetic model for both aripiprazole and its active metabolite, dehydroaripiprazole, in psychiatric patients and to identify to what extent the genetic polymorphisms of cytochrome P450 (CYP) enzymes contribute to the variability in pharmacokinetics (PK). METHODS A population pharmacokinetic analysis was performed using NONMEM software based on 141 plasma concentrations at steady state from 80 patients receiving multiple oral doses of aripiprazole (10,30 mg day,1). RESULTS A one-compartment model with first-order kinetics for aripiprazole and dehydroaripiprazole each was developed to describe simultaneously the concentration data. The absorption rate constant was fixed to 1.06 h,1. The typical value of apparent distribution volume of aripiprazole was estimated to be 192 l. Covariate analysis showed that CYP2D6 genetic polymorphisms significantly influenced the apparent clearance of aripiprazole (CL/F), reducing the interindividual variability on CL/F from 37.8% CV (coefficient of variation) to 30.5%. The CL/F in the CYP2D6 IMs was approximately 60% of that in CYP2D6 EMs having two functional alleles. Based on the CYP2D6 genotype, the metabolic ratios were calculated at 0.20,0.34. However, the plasma concentration : dose ratios of dehydroaripiprazole were not different across the CYP2D6 genotype. CONCLUSIONS This population pharmacokinetic model provided an adequate fit to the data for both aripiprazole and dehydroaripiprazole in psychiatric patients. The usefulness of CYP genotyping as an aid to select the starting dose should be further investigated. [source]