Estimation of Plasma Unbound Phenobarbital Concentration by Using Mixed Saliva

Nishihara, Kenji; Uchino, Katsuyoshi; Saitoh, Yurika; Honda, Yoshiyuki; Nakagawa, Fujio; Tamura, Zenzo

doi:10.1111/j.1528-1157.1979.tb04774.x

Cited by 26 publications

(10 citation statements)

References 18 publications

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“…Some prior studies of phenobarbital in newborns with seizures utilized free levels, because of concern about variable protein binding in critically ill newborns[6]. However, the free plasma phenobarbital level is tightly correlated to the total serum concentration [27, 28]. Finally, our study did not include premature infants, so the findings cannot be directly applied to that population.…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics of Phenobarbital in Infants With Neonatal Encephalopathy Treated With Therapeutic Hypothermia*

Shellhaas

Dillon

et al. 2013

Pediatric Critical Care Medicine

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Objective Phenobarbital is the first-line treatment for neonatal seizures. Many neonates with hypoxic ischemic encephalopathy (HIE) are treated with therapeutic hypothermia (TH) and about 40% have clinical seizures. Little is known about pharmacokinetics of phenobarbital in infants with HIE who undergo TH. The objective of this study was to determine the effect of TH on phenobarbital pharmacokinetics, taking into account maturational changes. Setting Level 3 neonatal intensive care unit. Patients Infants with HIE and suspected seizures, all treated with phenobarbital. Some of these infant also received treatment with TH. Interventions None. Design A retrospective cohort study of 39 infants with HIE treated with phenobarbital (20 were treated with TH and 19 were not). Measurements and main results Data were collected on phenobarbital plasma concentrations on 39 subjects with HIE with or without TH. Using nonlinear mixed-effects modeling, population pharmacokinetics of phenobarbital were developed with a total of 164 plasma concentrations. A one-compartment model best described the pharmacokinetics. The clearance (CL) of phenobarbital was linearly related to body weight and matured with increasing age with a maturation half-life of 22.1 days. TH did not influence the pharmacokinetic parameters of phenobarbital. Conclusions TH does not influence the CL of phenobarbital after accounting for weight and age. Standard phenobarbital dosing is appropriate for initial treatment of seizures in neonates with HIE treated with TH.

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Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics of Phenobarbital in Infants With Neonatal Encephalopathy Treated With Therapeutic Hypothermia*

Shellhaas

Dillon

et al. 2013

Pediatric Critical Care Medicine

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“…26,49,50,53,54,56,57,[73][74][75][134][135][136][137] Two studies have demonstrated that the distribution of phenobarbital into saliva depends on salivary pH 56,136 ; however, other studies have not found an effect of pH. A number of studies in both adults and children with epilepsy have demonstrated that phenobarbital distributes into saliva with saliva/total serum phenobarbital concentration ratios ranging 0.2-0.52, whereas the mean saliva/serum-free phenobarbital concentration ratios ranged 0.63-0.68.…”

Section: Saliva Tdm For Phenobarbitalmentioning

confidence: 99%

Therapeutic Drug Monitoring of Antiepileptic Drugs by Use of Saliva

Patsalos¹,

Berry²

2013

Therapeutic Drug Monitoring

170

126

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Blood (serum/plasma) antiepileptic drug (AED) therapeutic drug monitoring (TDM) has proven to be an invaluable surrogate marker for individualizing and optimizing the drug management of patients with epilepsy. Since 1989, there has been an exponential increase in AEDs with 23 currently licensed for clinical use, and recently, there has been renewed and extensive interest in the use of saliva as an alternative matrix for AED TDM. The advantages of saliva include the fact that for many AEDs it reflects the free (pharmacologically active) concentration in serum; it is readily sampled, can be sampled repetitively, and sampling is noninvasive; does not require the expertise of a phlebotomist; and is preferred by many patients, particularly children and the elderly. For each AED, this review summarizes the key pharmacokinetic characteristics relevant to the practice of TDM, discusses the use of other biological matrices with particular emphasis on saliva and the evidence that saliva concentration reflects those in serum. Also discussed are the indications for salivary AED TDM, the key factors to consider when saliva sampling is to be undertaken, and finally, a practical protocol is described so as to enable AED TDM to be applied optimally and effectively in the clinical setting. Overall, there is compelling evidence that salivary TDM can be usefully applied so as to optimize the treatment of epilepsy with carbamazepine, clobazam, ethosuximide, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, primidone, topiramate, and zonisamide. Salivary TDM of valproic acid is probably not helpful, whereas for clonazepam, eslicarbazepine acetate, felbamate, pregabalin, retigabine, rufinamide, stiripentol, tiagabine, and vigabatrin, the data are sparse or nonexistent.

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“…Studies on the detection of other barbiturates in oral fluid also have been reported including pentobarbital, 37 hexobarbital, 38,39 and phenobarbital. [40][41][42][43][44][45] September 29, 2006).…”

Section: Overviewmentioning

confidence: 99%

Interpretation of Oral Fluid Tests for Drugs of Abuse

Cone¹,

Huestis

2007

Annals of the New York Academy of Sciences

159

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Oral fluid testing for drugs of abuse offers significant advantages over urine as a test matrix. Collection can be performed under direct observation with reduced risk of adulteration and substitution. Drugs generally appear in oral fluid by passive diffusion from blood, but also may be deposited in the oral cavity during oral, smoked, and intranasal administration. Drug metabolites also can be detected in oral fluid. Unlike urine testing, there may be a close correspondence between drug and metabolite concentrations in oral fluid and in blood. Interpretation of oral fluid results for drugs of abuse should be an iterative process whereby one considers the test results in the context of program requirements and a broad scientific knowledge of the many factors involved in determining test outcome. This review delineates many of the chemical and metabolic processes involved in the disposition of drugs and metabolites in oral fluid that are important to the appropriate interpretation of oral fluid tests. Chemical, metabolic, kinetic, and analytic parameters are summarized for selected drugs of abuse, and general guidelines are offered for understanding the significance of oral fluid tests.

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Estimation of Plasma Unbound Phenobarbital Concentration by Using Mixed Saliva

Cited by 26 publications

References 18 publications

Population Pharmacokinetics of Phenobarbital in Infants With Neonatal Encephalopathy Treated With Therapeutic Hypothermia*

Population Pharmacokinetics of Phenobarbital in Infants With Neonatal Encephalopathy Treated With Therapeutic Hypothermia*

Therapeutic Drug Monitoring of Antiepileptic Drugs by Use of Saliva

Interpretation of Oral Fluid Tests for Drugs of Abuse

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