Abstract:
:Dosage adjustments can be difficult and time-consuming, especially for the non-specialist. The objective of this investigation was to obtain shortcut formulae to calculate dosage adjustments for (i) a drug obeying linear pharmacokinetics (i.e. first order) and given orally, by a continuous infusion or by an intermittent intravenous infusion; and (ii) a drug obeying Michaelis-Menten kinetics and given orally or by an intermittent intravenous infusion. Shortcut formulae are derived by assuming a steady-state model (e.g. one-compartment intermittent intravenous infusion) for a patient and drug and then dividing by the same equation, assuming a different dose and interval. The assumption underlying the division is that the patient's pharmacokinetic parameters do not change. The results obtained show that for drugs following linear pharmacokinetics and having the same dosage interval, the ratio of new dose : given dose is of course proportional to the ratio of desired steady-state concentration : measured steady-state concentration. If the interval is changed, then there are three variables: the dose, the steady-state concentration and the accumulation factor. The ratio of the doses is still proportional to the ratio of the steady-state concentrations but is also inversely proportional to the accumulation factors for the different dosage intervals. Furthermore, for intermittent infusions, the dosages calculated are equivalent to those obtained using the Sawchuk and Zaske method. With the shortcut formulae, it is more easily seen that most common dosage adjustments readily reduce to simple proportions or joint variation. These calculations can be quickly carried out with only the patient's terminal rate constant for linear pharmacokinetics and their Michaelis-Menten constant (Km) value for Michaelis-Menten kinetics. The methods are illustrated with actual patient examples.
journal_name
Clin Pharmacokinetjournal_title
Clinical pharmacokineticsauthors
Belloto RJ Jrdoi
10.2165/11313460-000000000-00000subject
Has Abstractpub_date
2009-01-01 00:00:00pages
555-60issue
9eissn
0312-5963issn
1179-1926pii
1journal_volume
48pub_type
杂志文章abstract::Sulphonylureas have remained the mainstay of oral therapy for type 2 (non-insulin-dependent) diabetes mellitus (NIDDM). They stimulate insulin release from pancreatic beta cells. Pharmacokinetic differences between the various sulphonylureas are of clinical importance in terms of the time to onset of action, timing of...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199834030-00001
更新日期:1998-03-01 00:00:00
abstract::Platelets contribute significantly to arterial-occlusive thrombosis, one of the major causes of death and disease throughout the world. Consequently, inhibiting platelet function is a potentially important therapeutic goal. Among agents that inhibit platelet function, ticlopidine shows a wide spectrum of antiplatelet ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199426050-00003
更新日期:1994-05-01 00:00:00
abstract::Despite progress in the treatment of metastatic colorectal cancer (mCRC) in the last 15 years, it is still a condition with a relatively low 5-year survival rate. Panitumumab, a fully human monoclonal antibody directed against the epidermal growth factor receptor (EGFR), is able to prolong survival in patients with mC...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-017-0590-9
更新日期:2018-04-01 00:00:00
abstract:INTRODUCTION:Renal impairment may have a significant impact on the pharmacokinetics of drugs. Ad hoc studies in subjects with renal impairment are required by the regulatory authorities to propose dose adjustments in these subjects, to find a dosing regimen able to provide a systemic exposure similar to those in subjec...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-017-0574-9
更新日期:2018-04-01 00:00:00
abstract::Aminoglycosides are important antibacterial agents for the treatment of serious infection. Evidence suggests that high peak plasma concentrations must be achieved early in the course of treatment if these agents are to be effective, but prolonged high concentrations may cause ototoxicity and nephrotoxicity. Peak plasm...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199427010-00004
更新日期:1994-07-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Daclatasvir is a potent, pangenotypic once-daily hepatitis C virus (HCV) NS5A inhibitor that is approved for the treatment of chronic HCV infection. The objective of this analysis was to characterize the pharmacokinetics of daclatasvir in subjects with chronic HCV infection. METHODS:A populati...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-016-0504-2
更新日期:2017-10-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Dosing of therapeutic monoclonal antibodies (mAbs) is often based on body size, with the perception that body size-based dosing would reduce inter-subject variability in drug exposure. However, most mAbs are target specific with a relatively large therapeutic window and generally a small contri...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/11596370-000000000-00000
更新日期:2012-02-01 00:00:00
abstract:OBJECTIVE:To assess the differences between patients with hepatic insufficiency and healthy subjects with regard to the pharmacokinetics, cardiac safety and overall safety of ebastine and its active metabolite carebastine. DESIGN:Open-label parallel-group study. PARTICIPANTS:24 patients with varying degrees of hepati...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章
doi:10.2165/00003088-200443020-00004
更新日期:2004-01-01 00:00:00
abstract::Voriconazole is both a substrate and a potent inhibitor of cytochrome P450 (CYP) 3A. It has a high bioavailability and non-linear pharmacokinetics. We investigated the pharmacokinetics and metabolism of 50 mg and 400 mg doses of intravenous and oral voriconazole in 14 healthy volunteers. Concurrently, we determined sy...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章
doi:10.1007/s40262-016-0416-1
更新日期:2016-12-01 00:00:00
abstract::Pegfilgrastim is a sustained-duration form of filgrastim, a recombinant methionyl form of human granulocyte colony-stimulating factor (G-CSF), to which a 20 kDa polyethylene glycol molecule is covalently bound to the N-terminal methionine residue. Similar to filgrastim, pegfilgrastim increases the proliferation and d...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/11586040-000000000-00000
更新日期:2011-05-01 00:00:00
abstract::Population pharmacokinetic modelling is widely used within the field of clinical pharmacology as it helps to define the sources and correlates of pharmacokinetic variability in target patient populations and their impact upon drug disposition; and population pharmacokinetic modelling provides an estimation of drug pha...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/BF03261932
更新日期:2012-09-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Bosentan is a competitive antagonist on endothelin receptor A and B (ETA and ETB), displacing the endogenous binding partner endothelin-1 (ET-1) from its binding sites. After administration of escalating single doses of 10-750 mg as an intravenous (i.v.) infusion, bosentan showed dose-dependen...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-017-0534-4
更新日期:2017-12-01 00:00:00
abstract::There is a considerable range in the dose of many drugs that is required to produce a given pharmacological effect in an individual patient. This individual variation in dose requirement is sometimes reflected in the wide scatter in the steady state plasma concentration that follows the same oral dose of a drug given ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-197702010-00004
更新日期:1977-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Currently, the majority of the surgical procedures performed in paediatric hospitals are done on a day care basis, with post-operative pain being managed by caregivers at home. Pain after discharge of these post-operative children has historically been managed with oral codeine in combination ...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s40262-015-0256-4
更新日期:2015-10-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Clearance is an important pharmacokinetic concept for scaling dosage, understanding the risks of drug-drug interactions and environmental risk assessment in children. Accurate clearance scaling to children requires prior knowledge of adult clearance mechanisms and the age-dependence of physiolo...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-200645070-00004
更新日期:2006-01-01 00:00:00
abstract::Pharmacological treatment of patients with Alzheimer's disease is becoming more important, as evidenced by the number of drugs being developed in different countries. It has been shown in the majority of clinical trials that cholinesterase inhibitors, such as tacrine (tetrahydroaminoacridine), are able to induce benef...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199529020-00005
更新日期:1995-08-01 00:00:00
abstract::In the treatment of patients with Parkinson's disease, apomorphine has an established place as a back-up therapy if other antiparkinsonian drugs, such as levodopa and oral dopamine agonists, have not controlled the existing response fluctuations. Apomorphine is a synthetic derivative of morphine, with a totally distin...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199937030-00004
更新日期:1999-09-01 00:00:00
abstract::Doxycycline and minocycline are second-generation tetracyclines. They are readily absorbed, distributed throughout the organism as a function of their lipophilicity and eliminated in both the urine and the faeces. The influence of age, renal disease, malnutrition and hyperlipidaemia is reviewed, together with the main...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198815060-00001
更新日期:1988-12-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Tegafur is an oral fluorouracil prodrug used in the treatment of colorectal cancer. The aim of this phase II, crossover, bioequivalence study was to compare the pharmacokinetics (primary objective) and tolerability (secondary objective) of tegafur-uracil (UFT) given as three daily doses (tid, r...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,随机对照试验
doi:10.2165/00003088-200746110-00003
更新日期:2007-01-01 00:00:00
abstract::Vedolizumab is a humanized anti-α4β7 integrin monoclonal antibody that selectively blocks trafficking of memory T cells to inflamed gut tissue by inhibiting the α4β7-mucosal addressin cell adhesion molecule-1 (MAdCAM-1) interaction. Approved for treating patients with moderately to severely active ulcerative colitis (...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-017-0546-0
更新日期:2017-11-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Daclizumab high-yield process (DAC HYP) is a humanized monoclonal antibody that selectively blocks the α-subunit (CD25) of the high-affinity interleukin-2 receptors, and has shown robust efficacy as a treatment for multiple sclerosis (MS). This work quantitatively characterized the relationship...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40262-015-0305-z
更新日期:2016-01-01 00:00:00
abstract::Thienopyridines are inactive prodrugs that are converted in vivo to active metabolites, which irreversibly bind to and inactivate platelet P2Y(12) receptors, and inhibit platelet activation and aggregation. Prasugrel is a third-generation thienopyridine, recently approved for prevention of thrombotic cardiovascular co...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/11537820-000000000-00000
更新日期:2010-12-01 00:00:00
abstract::Lignocaine is widely used as a local anaesthetic and antiarrhythmic drug. It is commonly administered to patients with acute myocardial infarction as prophylaxis for ventricular fibrillation, although its efficacy in preventing primary ventricular fibrillation is still debated. Toxicity, sometimes with serious clinica...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-197803030-00001
更新日期:1978-05-01 00:00:00
abstract::Drugs from a wide range of pharmacological classes are commonly given to women in childbirth, either for a maternal effect or a fetal/neonatal effect. A number of striking physiological and biochemical changes occur during labour and delivery that might alter drug kinetics. The rate of drug absorption from the gastroi...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198005040-00003
更新日期:1980-07-01 00:00:00
abstract:OBJECTIVE:To assess any pharmacokinetic interactions between loperamide and saquinavir. DESIGN:Double-blind, double-dummy, randomised, placebo-controlled, three-way crossover trial. PARTICIPANTS:Twelve healthy male and female volunteers, aged 24-46 years. METHODS:Saquinavir and loperamide pharmacokinetics were deter...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2165/00003088-200443140-00004
更新日期:2004-01-01 00:00:00
abstract::Pregnancy is a specific dynamic state, and the potential usefulness of caring for a disorder in the fetus or the mother is now well established. Previously, pregnant women have been excluded from clinical trials, therefore only a few studies concerning evaluation of the pregestational metabolism or transplacental tran...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199528020-00006
更新日期:1995-02-01 00:00:00
abstract:BACKGROUND:Fast-acting insulin aspart (faster aspart) is an ultra-fast-acting formulation of insulin aspart (IAsp). This post hoc analysis investigated the pharmacokinetics of faster aspart versus IAsp, measured as free or total IAsp, and the relationship between anti-IAsp antibodies and the pharmacokinetics/pharmacody...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s40262-018-0718-6
更新日期:2019-05-01 00:00:00
abstract::The ability of a new multiple-dose non-linear regression analysis program to predict steady-state aminoglycoside peak and trough serum concentrations was evaluated. 30 patients receiving either amikacin (7), gentamicin (10) or tobramycin (13) were studied. A standard method of prediction which requires the collection ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-198308050-00006
更新日期:1983-09-01 00:00:00
abstract::The effects of anaesthesia and surgery on the pharmacokinetics of ketobemidone were studied in 12 patients. Plasma ketobemidone concentrations were assayed with a mass-fragmentographic method. The peroperative Vd(area) was 5.9 +/- 2.6L/kg and the terminal half-life was 3.9 +/- 1.7 h. In the postoperative period Vd(are...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-198207030-00005
更新日期:1982-05-01 00:00:00
abstract::Short-term antimanic therapy with lithium and relapse-repressive, so-called "prophylactic" long-term therapy with lithium, may present clinical problems which demand an understanding of two cardinal properties of this form of therapy--the need to individualise the dose and the recognition that successful therapy invol...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-197702020-00001
更新日期:1977-03-01 00:00:00