A clinically relevant review of tizanidine hydrochloride dose relationships to pharmacokinetics, drug safety and effectiveness in healthy subjects and patients

Henney, Herbert R.; Runyan, Jacob D.

doi:10.1111/j.1742-1241.2007.01660.x

Cited by 40 publications

(30 citation statements)

References 27 publications

(58 reference statements)

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“…The need to personalize drug dosing is especially critical, and difficult, when prescribing drugs with narrow therapeutic indices, indicative of a small ratio between the toxic dose and the therapeutic dose of a drug. [1,2] Many medications exhibit wide interindividual variability in clinical response. For instance, the dosage of oral morphine needed to adequately reduce pain can range from <30 mg/day to 15 g/day.…”

Section: Pharmacodynamic and Pharmacokinetic Variabilitymentioning

confidence: 99%

Pharmacokinetic Variability of Long-Acting Stimulants in the Treatment of Children and Adults with Attention-Deficit Hyperactivity Disorder

Ermer

Adeyi

Pucci³

2010

CNS Drugs

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Methylphenidate- and amfetamine-based stimulants are first-line pharmacotherapies for attention-deficit hyperactivity disorder, a common neurobehavioural disorder in children and adults. A number of long-acting stimulant formulations have been developed with the aim of providing once-daily dosing, employing various means to extend duration of action, including a transdermal delivery system, an osmotic-release oral system, capsules with a mixture of immediate- and delayed-release beads, and prodrug technology. Coefficients of variance of pharmacokinetic measures can estimate the levels of pharmacokinetic variability based on the measurable variance between different individuals receiving the same dose of stimulant (interindividual variability) and within the same individual over multiple administrations (intraindividual variability). Differences in formulation clearly impact pharmacokinetic profiles. Many medications exhibit wide interindividual variability in clinical response. Stimulants with low levels of inter- and intraindividual variability may be better suited to provide consistent levels of medication to patients. The pharmacokinetic profile of stimulants using pH-dependent bead technology can vary depending on food consumption or concomitant administration of medications that alter gastric pH. While delivery of methylphenidate with the transdermal delivery system would be unaffected by gastrointestinal factors, intersubject variability is nonetheless substantial. Unlike the beaded formulations and, to some extent (when considering total exposure) the osmotic-release formulation, systemic exposure to amfetamine with the prodrug stimulant lisdexamfetamine dimesylate appears largely unaffected by such factors, likely owing to its dependence on systemic enzymatic cleavage of the precursor molecule, which occurs primarily in the blood involving red blood cells. The high capacity but as yet unidentified enzymatic system for conversion of lisdexamfetamine dimesylate may contribute to its consistent pharmacokinetic profile. The reasons underlying observed differential responses to stimulants are likely to be multifactorial, including pharmacodynamic factors. While the use of stimulants with low inter- and intrapatient pharmacokinetic variability does not obviate the need to titrate stimulant doses, stimulants with low intraindividual variation in pharmacokinetic parameters may reduce the likelihood of patients falling into subtherapeutic drug concentrations or reaching drug concentrations at which the risk of adverse events increases. As such, clinicians are urged both to adjust stimulant doses based on therapeutic response and the risk for adverse events and to monitor patients for potential causes of pharmacokinetic variability.

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Section: Pharmacodynamic and Pharmacokinetic Variabilitymentioning

confidence: 99%

Pharmacokinetic Variability of Long-Acting Stimulants in the Treatment of Children and Adults with Attention-Deficit Hyperactivity Disorder

Ermer

Adeyi

Pucci³

2010

CNS Drugs

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“…Tizanidine appears to act predominantly presynaptically in the spinal cord by reducing release of the excitatory amino acid glutamate and aspartate from the presynaptic terminal of spinal interneurons and it may facilitate the action of the inhibitory neurotransmitter glycine. [1011]…”

Section: Introductionmentioning

confidence: 99%

Limitations and obstacles of the spontaneous adverse drugs reactions reporting: Two “challenging” case reports

Palleria

Leporini

Chimirri

et al. 2013

Journal of Pharmacology and Pharmacotherapeutics

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Introduction:Nowadays, based on several epidemiological data, iatrogenic disease is an emerging public health problem, especially in industrialized countries. Adverse drugs reactions (ADRs) are extremely common and, therefore, clinically, socially, and economically worthy of attention. Spontaneous reporting system for suspected ADRs represents the cornerstone of the pharmacovigilance, because it allows rapid detection of potential alarm signals related to drugs use. However, spontaneous reporting system shows several limitations, which are mainly related to under-reporting. In this paper, we describe two particular case reports, which emphasize some reasons of under-reporting and other common criticisms of spontaneous reporting systems.Materials and Methods:We performed a computer-aided search of Medline, PubMed, Embase, Cochrane library databases, national and international databases of suspected ADRs reports in order to identify previous published case reports and spontaneous reports about the ADRs reviewed in this paper, and to examine the role of suspected drugs in the pathogenesis of the described adverse reactions.Results:First, we reported a case of tizanidine-induced hemorrhagic cystitis. In the second case report, we presented an episode of asthma exacerbation after taking bimatoprost. Through the review of these two cases, we highlighted some common criticisms of spontaneous reporting systems: under-reporting and false causality attribution.Discussion and Conclusion:Healthcare workers sometimes do not report ADRs because it is challenging to establish with certainty the causal relationship between drug and adverse reaction; however, according to a key principle of pharmacovigilance, it is always better to report even a suspicion to generate an alarm in the interest of protecting public health.

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“…Tizanidine is an α 2 ‐adrenergic agonist approved for therapy of muscle spasm and other conditions. It is frequently prescribed, off‐label, for suppression of the symptoms associated with opiate withdrawal during detoxification . Because some individuals with HIV infection may also suffer from and be treated for opioid abuse, the likelihood that tizanidine and efavirenz may be coadministered is high.…”

Section: Discussionmentioning

confidence: 99%

CYP2B6 Genotype‐Dependent Inhibition of CYP1A2 and Induction of CYP2A6 by the Antiretroviral Drug Efavirenz in Healthy Volunteers

Metzger

Dave

Kreutz

et al. 2019

Clinical Translational Sci

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We investigated the effect of efavirenz on the activities of cytochrome P450 (CYP)1A2, CYP2A6, xanthine oxidase (XO), and N‐acetyltransferase 2 (NAT2), using caffeine as a probe. A single 150 mg oral dose of caffeine was administered to healthy volunteers (n = 58) on two separate occasions; with a single 600 mg oral dose of efavirenz and after treatment with 600 mg/day efavirenz for 17 days. Caffeine and its metabolites in plasma and urine were quantified using liquid chromatography/tandem‐mass spectrometry. DNA was genotyped for CYP2B6*4 (785A>G), CYP2B6*9 (516G>T), and CYP2B6*18 (983T>C) alleles using TaqMan assays. Relative to single‐dose efavirenz treatment, multiple doses of efavirenz decreased CYP1A2 (by 38%) and increased CYP2A6 (by 85%) activities (P < 0.05); XO and NAT2 activities were unaffected. CYP2B6*6*6 genotype was associated with lower CYP1A2 activity following both single and multiple doses of efavirenz. No similar association was noted for CYP2A6 activity. This is the first report showing that efavirenz reduces hepatic CYP1A2 and suggesting chronic efavirenz exposure likely enhances the elimination of CYP2A6 substrates. This is also the first to report the extent of efavirenz–CYP1A2 interaction may be efavirenz exposure‐dependent and CYP2B6 genotype‐dependent.

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A clinically relevant review of tizanidine hydrochloride dose relationships to pharmacokinetics, drug safety and effectiveness in healthy subjects and patients

Cited by 40 publications

References 27 publications

Pharmacokinetic Variability of Long-Acting Stimulants in the Treatment of Children and Adults with Attention-Deficit Hyperactivity Disorder

Pharmacokinetic Variability of Long-Acting Stimulants in the Treatment of Children and Adults with Attention-Deficit Hyperactivity Disorder

Limitations and obstacles of the spontaneous adverse drugs reactions reporting: Two “challenging” case reports

CYP2B6 Genotype‐Dependent Inhibition of CYP1A2 and Induction of CYP2A6 by the Antiretroviral Drug Efavirenz in Healthy Volunteers

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