Suicide by buflomedil HCl: a case report

Neri, Carla; Barbareschi, Mattia; Turrina, Stefania; Leo, Domenico De

doi:10.1016/j.jcfm.2003.10.004

Cited by 8 publications

(3 citation statements)

References 2 publications

(1 reference statement)

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“…The concentrations were estimated by solving the ordinary differential equation system describing the compartmental pharmacokinetic model, using MATLAB and the solver ode45. The peak concentration reached after 10 days of treatment was calculated for each simulated patient and compared to buflomedil levels observed in toxic events as reported in the literature [12,13,22,40]. A threshold concentration of 10 mg/L was set as the value from which potentially serious clinical consequences could occur [22].…”

Section: Methodsmentioning

confidence: 99%

“…Intoxication with buflomedil is characterized by severe cardiovascular and neurologic effects and can be lethal. Overdosing caused by self-poisoning or renal impairment is considered a major risk factor for severe intoxication with buflomedil [12][13][14][15][16][17][18][19][20][21][22]. Severe intoxications have been associated with drug levels superior to 10 mg/L [22].…”

Section: Introductionmentioning

confidence: 99%

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The value of population pharmacokinetics and simulation for postmarketing safety evaluation of dosing guidelines for drugs with a narrow therapeutic index: buflomedil as a case study

Bourguignon¹,

Ducher²,

Matanza³

et al. 2011

Fundamemntal Clinical Pharma

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Population pharmacokinetics and simulation techniques currently play an important role in new drug development. This paper illustrates the potential value of those methods in postmarketing safety assessment, using buflomedil in elderly patients as an example. We retrospectively assessed the risk of buflomedil overdosing associated with the latest dosing recommendations of the French Drug Agency (AFSSAPS). First, buflomedil concentrations measured in 24 elderly patients were analysed with a nonparametric population approach. Then, the pharmacokinetic model was used to perform a 1000-patient Monte Carlo simulation for the two recommended buflomedil dosage regimens. The maximum concentrations calculated after 10 days of therapy were compared with levels observed in reported cases of toxicity to assess the probability of overdosing. A three-compartment model best fit concentration data. Population predictions showed little bias (-0.14 mg/L) and good precision (8.73 mg(2) /L(2)). Overall results of the simulation study showed that the application of the two recommended dosage regimens of buflomedil was associated with overdosing (C(max)> 10 mg/L) and potential toxicity in 2.9% of geriatric patients. In patients with mild renal impairment, who may receive the higher-dosage regimen by therapeutic error, the probability of overdosing was 6.2%. Despite specific dosing recommendations in case of renal impairment, this study shows that the use of buflomedil could be associated with significant risk of overdosing in geriatric patients. Such results might have enhanced decision-making when buflomedil safety was reassessed by AFSSAPS in 2006. The retrospective case of buflomedil illustrates how these methods may be valuable in postmarketing safety evaluation of potentially toxic drugs.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The value of population pharmacokinetics and simulation for postmarketing safety evaluation of dosing guidelines for drugs with a narrow therapeutic index: buflomedil as a case study

Bourguignon¹,

Ducher²,

Matanza³

et al. 2011

Fundamemntal Clinical Pharma

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“…There are 401 case reports in the buflomedil database (1975-2011) which fall into this category and represent people who have taken deliberate overdoses, and include those cases described as suicide attempt, completed suicide and IOD. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] Of the 401 IOD cases, 156 were males, 223 females and 22 with gender not recorded. The ages of IOD people…”

Section: Case Reportsmentioning

confidence: 99%