Michael T. Kelley

Children´s Hospital Association, Overland Park, Kansas, United States

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Publications (12)37.94 Total impact

  • D A Wiles · J L Russell · K R Olson · P D Walson · M Kelley
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    ABSTRACT: Lindane is a possible carcinogen with known teratogenicity and immunologic and neurotoxic properties. Despite reports of seizures, coma, and death associated with its use as well as banning of its environmental use by the Environmental Protection Agency (EPA), the US Food and Drug Administration (FDA) still allows treatment with lindane as a second-line scabicide and pediculicide. We present a case of a massive suicidal ingestion of lindane in which the patient survived the ingestion, though he did expire shortly thereafter from an unrelated cause pre-discharge. Pharmacokinetic analysis of serum lindane concentrations was performed with Phoenix® WinNONLIN®. The estimated distribution half-life for lindane was 10.3 h, and the terminal half-life was 162.9 h, much longer than the previously reported terminal half-life of 25-36 h. Because of this long half-life, repeated lindane exposures may lead to accumulation of lindane in the tissues. After overdose, toxicity may be delayed and full recovery may be prolonged.
    No preview · Article · May 2014 · Journal of medical toxicology: official journal of the American College of Medical Toxicology
  • Marcel J. Casavant · Philip D. Walson · Michael Kelley

    No preview · Article · May 2013 · Clinical Therapeutics
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    ABSTRACT: BACKGROUND: Because of practical problems and ethical concerns, few studies of the pharmacokinetics (PK) of acetaminophen (ACET) in infants have been published. OBJECTIVE: The goal of this study was to compare the PK of an ACET rectal suppository with a commercially available ACET elixir to complete a regulatory obligation to market the suppository. This study was not submitted previously because of numerous obstacles related to both the investigators and the commercial entities associated with the tested product. METHODS: Thirty infants (age 3-36 months) prescribed ACET for either fever, pain, or postimmunization prophylaxis of fever and discomfort were randomized to receive a single 10- to 15-mg/kg ACET dose either as the rectal suppository or oral elixir. Blood was collected at selected times for up to 8 hours after administration. ACET concentrations were measured by using a validated HPLC method, and PK behavior and bioavailability were compared for the 2 preparations. RESULTS: All 30 infants enrolled were prescribed ACET for postimmunization prophylaxis. PK samples were available in 27 of the 30 enrolled infants. Subject enrollment (completed in January 1995) was rapid (8.3 months) and drawn entirely from a vaccinated infant clinic population. There were no statistically significant differences between the subjects (elixir, n = 12; suppository, n = 15) in either mean (SD) age (10.0 [6.3] vs 12.4 [8.1] months), weight (8.6 [2.3] vs 9.4 [2.4] kg), sex (7 of 12 males vs 7 of 15 males), or racial distribution (5 white, 5 black, and 2 biracial vs 4 white and 11 black) between the 2 dosing groups (oral vs rectal, respectively). The oral and rectal preparations produced similar, rapid peak concentrations (T(max), 1.16 vs 1.17 hours; P = 0.98) and elimination t(½) (1.84 vs 2.10 hours; P = 0.14), respectively. No statistically significant differences were found between either C(max) (7.65 vs 5.68 μg/mL) or total drug exposure (AUC(0-∞), 23.36 vs 20.45 μg-h/mL) for the oral versus rectal preparations. There were no serious treatment-related effects noted. Delays in submitting this work for publication were the result of a number of investigator and sponsor issues despite the study's positive outcome. CONCLUSIONS: No statistically significant differences were found between the rates or extent of absorption of the suppository and elixir preparations in this small, infant population. Both preparations were well tolerated. Vaccinated infants were a useful population in which to conduct a PK study of this antipyretic, analgesic product. Delays in publishing pediatric trials can occur as a result of a number of issues even when results are positive.
    Full-text · Article · Jan 2013 · Clinical Therapeutics
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    ABSTRACT: Poison Control Centers follow the acetylsalicylic acid (ASA) treatment guideline to manage unintentional ingestions of topical methyl salicylate liniments. For example, one teaspoon of 30% methyl salicylate cream such as Ben Gay provides an "ASA equivalent dose" of 180 mg/kg for a 10 kg child. The ASA treatment guideline advises emesis with syrup of Ipecac and 24 h home followup for this dose. Both the ASA conversion factor to yield the ASA equivalent dose and the treatment guideline assume 100% bioavailability of the salicylate. The nature of this topical dosage product led the investigators to expect less than complete absorption of methyl salicylate. To compare plasma concentrations of salicylate from ingested methyl salicylate cream with plasma concentrations of salicylate from ingested oil of wintergreen. Four adult volunteers consented to an open label, four-way crossover design, with randomization to the following treatments: 1 mL Oil of Wintergreen, U.S.P., 6.7 g of Ben Gay 15% and 20 g of Ben Gay 15% and also to hold 5 g of Ben Gay 15% cream in the buccal cavity for 1 minute and then expectorate. Plasma was collected for salicylate determination, and the results analyzed with a noncompartmental pharmacokinetic model. No plasma salicylate was detected after buccal treatment phase. Relative bioavailability for the low-dose treatment was 0.5 compared to oil of wintergreen. Plasma salicylate concentrations from methyl salicylate cream are not equal to those achieved after ingestion of oil of wintergreen. Dosage formulation must be considered when predicting toxicity.
    No preview · Article · Feb 2003 · Journal of toxicology. Clinical toxicology
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    ABSTRACT: Background. Poison Control Centers follow the acetylsalicylic acid (ASA) treatment guideline to manage unintentional ingestions of topical methyl salicylate liniments. For example, one teaspoon of 30% methyl salicylate cream such as Ben Gay® provides an “ASA equivalent dose” of 180 mg/kg for a 10 kg child. The ASA treatment guideline advises emesis with syrup of Ipecac and 24 h home followup for this dose. Both the ASA conversion factor to yield the ASA equivalent dose and the treatment guideline assume 100% bioavailability of the salicylate. The nature of this topical dosage product led the investigators to expect less than complete absorption of methyl salicylate. Objective. To compare plasma concentrations of salicylate from ingested methyl salicylate cream with plasma concentrations of salicylate from ingested oil of wintergreen. Methods. Four adult volunteers consented to an open label, four-way crossover design, with randomization to the following treatments: 1 mL Oil of Wintergreen, U.S.P., 6.7 g of Ben Gay® 15% and 20 g of Ben Gay® 15% and also to hold 5 g of Ben Gay® 15% cream in the buccal cavity for 1 minute and then expectorate. Plasma was collected for salicylate determination, and the results analyzed with a noncompartmental pharmacokinetic model. Results. No plasma salicylate was detected after buccal treatment phase. Relative bioavailability for the low-dose treatment was 0.5 compared to oil of wintergreen. Conclusion. Plasma salicylate concentrations from methyl salicylate cream are not equal to those achieved after ingestion of oil of wintergreen. Dosage formulation must be considered when predicting toxicity.
    No preview · Article · Jan 2003 · Clinical Toxicology
  • Michael T. Kelley · Philip D. Walson · Shareen Cox · Leon J. Dusci
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    ABSTRACT: Information about the pharmacokinetics of felbamate in children is limited. Even though it is claimed that monitoring of felbamate concentrations is unnecessary, many neurologists have requested therapeutic drug monitoring (TDM) for various reasons. This study used the NONMEM program to describe the pharmacokinetics and the influence of other anticonvulsants on the pharmacokinetics of felbamate. Felbamate, carbamazepine (CBZ), phenytoin (PHY), valproate (VPA), and barbiturate serum levels were obtained by our TDM service as requested by the clinician. The clearance and volume of distribution of felbamate were 41.1 ml/h/kg and 908 ml/kg, respectively. CBZ and PHY increased the clearance 49 and 40% while VPA decreased it 21%. Barbiturate had no significant effect. Clearance also decreased with age.
    No preview · Article · Mar 1997 · Therapeutic Drug Monitoring
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    M. T. Kelley · P. D. Walson · S. Cox
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    ABSTRACT: Clinical Pharmacology & Therapeutics (1996) 59, 213–213; doi: 10.1038/sj.clpt.1996.352
    Full-text · Article · Feb 1996 · Clinical Pharmacology &#38 Therapeutics
  • Michael T. Kelley · Dr Philip D. Walson · John R. Hayes · James H. Edge
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    ABSTRACT: The increasing use of ibuprofen for the treatment of fever in children has caused concern about possible toxic effects. In susceptible adults ibuprofen has caused kidney dysfunction. While it is unlikely that a child with known kidney disease would be given ibuprofen, many children with febrile illnesses are dehydrated. This report presents an analysis of pre- and poststudy observations from 2 clinical trials that compared the antipyretic effects of ibuprofen and paracetamol in 180 otherwise healthy febrile children. In the first trial, 119 febrile children received a single oral dose of either placebo, paracetamol or one of 2 doses of ibuprofen. In the second trial, 61 children received either paracetamol or one of 3 doses of ibuprofen orally every 6 hours for between 24 and 48 hours. Pre- and poststudy blood chemistries, urine and vital signs were analysed. Liberal statistical analyses identified few adverse effects and no clinically significant adverse effects. Statistically significant changes were all consistent with poststudy haemodilution (rehydration) except for blood urea nitrogen (BUN). Poststudy BUN concentrations were statistically significantly greater than prestudy values for paracetamol- and ibuprofen-treated patients. However, none of the BUN results were abnormal or clinically important. Although this study found no clinically significant adverse effects, much larger studies are necessary to establish safety in the general population.
    No preview · Article · Jul 1993 · Drug Investigation
  • Anthony Restuccio · Mary Ellen Mortensen · Michael T. Kelley
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    ABSTRACT: A 45-year-old white man ingested approximately two cups of boric acid crystals dissolved in water in a suicide attempt. Nausea, vomiting, greenish diarrhea, and dehydration occurred shortly thereafter. Two days later, he presented to the hospital with hypotension, metabolic acidosis, oliguric renal failure, a generalized erythematous rash, and several superficial skin abrasions. His condition failed to improve despite intravenous fluids and vasopressors. He later developed atrial fibrillation with a rapid ventricular response and could not be converted to a sinus rhythm. This rhythm deteriorated to electromechanical dissociation, and the patient died 17 hours after admission. The urine and whole blood boric acid concentrations approximately 52 hours after ingestion were 160 and 42 mg/dL, respectively. These results are equivalent to urine and blood boron concentrations of 28 and 7 mg/dL, respectively. A postmortem urine boron concentration was 29.4 mg/dL. The autopsy report listed boron toxicity as the cause of death. This is the only adult reported to die from acute boric acid ingestion in recent years and may be atypical since the patient was untreated for 3 days and presented with dehydration and renal function impairment. This case suggests that lack of adequate urine flow and dehydration increases the risk of boron toxicity.
    No preview · Article · Dec 1992 · American Journal of Emergency Medicine
  • Tuan A Luu · MD Michael T Kelley · Jean A Strauch · Konstantino Avradopoulos
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    ABSTRACT: A 40-year-old woman who ingested a 35% hydrogen peroxide solution presented to the emergency department with abdominal pain. Acute abdominal series showed gas in the portal vein system. The patient was admitted and treated conservatively. She was released after five days in the hospital with no major sequelae.
    No preview · Article · Dec 1992 · Annals of Emergency Medicine
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    ABSTRACT: The pharmacokinetics of racemic ibuprofen and its stereoisomers have been described in adults, but little has been reported for children. The pharmacodynamics of acetaminophen and ibuprofen have not been well described in either adults or children. Children (N = 39; age range, 11 months to 11 1/2 years) were randomly selected to receive a single dose of either 6 mg/kg of liquid ibuprofen or 10 to 15 mg/kg of liquid acetaminophen (mean +/- dose given, 11.6 +/- 0.7). Pharmacokinetic and pharmacodynamic analyses were performed with temperature as the effect parameter and mean acetaminophen, total ibuprofen, and ibuprofen stereoisomer concentrations over time. Time of maximum serum concentrations for ibuprofen was 54.05 minutes versus 27.0 minutes for acetaminophen, time to maximum temperature decrease was 183 minutes for ibuprofen and 133 minutes for acetaminophen. Temperature reduction for the ibuprofen dose was significantly different than that of the acetaminophen dose at later time points (240, 300, 360, 420, and 480 minutes). Further pharmacokinetic-pharmacodynamic studies with use of individual ibuprofen stereoisomers and other dosing regimens are indicated.
    Full-text · Article · Sep 1992 · Clinical Pharmacology &#38 Therapeutics
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    ABSTRACT: We describe a near-fatal case of encainide toxicity in a 6-month-old infant who reportedly ingested a single 25-mg tablet. Within 30 minutes he had a wide-complex sinus tachycardia (QRS, 0.16 second) and then acutely decompensated with the development of ventricular tachycardia. Electroshock cardioversion (probably synchronized but not documented) was performed, but the ventricular tachycardia returned. Intraosseous fluids, sodium bicarbonate, and phenytoin were administered, and defibrillation was performed. The resultant wide-complex tachyarrhythmia gradually normalized. Serum encainide and metabolite concentrations obtained at the time of resuscitation (60 minutes after ingestion) exceeded the therapeutic adult range. History and blood concentration data were consistent with ingestion of as little as a single 25-mg tablet, which was nearly fatal to this child.
    No preview · Article · Sep 1992 · Annals of Emergency Medicine