Clinical Pharmacology and Efficacy of Ticarcillin in Infants and Children

PEDIATRICS ◽  
1978 ◽  
Vol 61 (6) ◽  
pp. 858-863 ◽  
Author(s):  
John D. Nelson ◽  
Helen Kusmiesz ◽  
Sharon Shelton ◽  
Edythe Woodman
Keyword(s):  
Pediatric Patients ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Older Children ◽  
Efficacy Data ◽  
Suspected Sepsis ◽  
Suitable Alternative ◽  
Young Infants ◽  
Limited Efficacy ◽  
Pseudomonas Infection

Ticarcillin was evaluated in 82 neonates and young infants with suspected sepsis and in 16 older children with chronic Pseudomonas infection of the mastoids. The infants also received kanamycin. Individual ticarcillin doses of 75 or 100 mg/kg were given every four, six, or eight hours by intramuscular injection or by a 30-minute intravenous infusion. Mean plasma concentrations one hour after a dose were from 125 to 189 µg/ml, depending on dosage, age, and maturity. Mean plasma half-lives were approximately 5 hours in the first week of life, 2 hours in infants from 1 to 8 weeks, and 0.9 hours in older children. Volume of distribution was approximately twice as great in infants as in children, and plasma clearance rates correlated inversely with age. Limited efficacy data suggest that ticarcillin is a suitable alternative to ampicillin or carbenicillin, when given concurrently with an aminoglycoside, for newborn infections. When given for several days before mastoidectomy and tympanoplasty, ticarcillin sterilized the mastoids in the majority of patients. A new dosage schedule for ticarcillin in pediatric patients is proposed.

scholarly journals Effects of Body Size and Gender on the Population Pharmacokinetics of Artesunate and Its Active Metabolite Dihydroartemisinin in Pediatric Malaria Patients

2013 ◽  
Vol 57 (12) ◽  
pp. 5889-5900 ◽  
Author(s):  
Carrie A. Morris ◽  
Beesan Tan ◽  
Stephan Duparc ◽  
Isabelle Borghini-Fuhrer ◽  
Donald Jung ◽  
...  
Keyword(s):  
Body Size ◽  
Active Metabolite ◽  
Allometric Scaling ◽  
Pediatric Patients ◽  
Volume Of Distribution ◽  
Gender Effects ◽  
Older Children ◽  
Scaling Model ◽  
And Gender ◽  
Using Data

ABSTRACTDespite the important role of the antimalarial artesunate and its active metabolite dihydroartemisinin (DHA) in malaria treatment efforts, there are limited data on the pharmacokinetics of these agents in pediatric patients. This study evaluated the effects of body size and gender on the pharmacokinetics of artesunate-DHA using data from pediatric and adult malaria patients. Nonlinear mixed-effects modeling was used to obtain a base model consisting of first-order artesunate absorption and one-compartment models for artesunate and for DHA. Various methods of incorporating effects of body size descriptors on clearance and volume parameters were tested. An allometric scaling model for weight and a linear body surface area (BSA) model were deemed optimal. The apparent clearance and volume of distribution of DHA obtained with the allometric scaling model, normalized to a 38-kg patient, were 63.5 liters/h and 65.1 liters, respectively. Estimates for the linear BSA model were similar. The 95% confidence intervals for the estimated gender effects on clearance and volume parameters for artesunate fell outside the predefined no-relevant-clinical-effect interval of 0.75 to 1.25. However, the effect of gender on apparent DHA clearance was almost entirely contained within this interval, suggesting a lack of an influence of gender on this parameter. Overall, the pharmacokinetics of artesunate and DHA following oral artesunate administration can be described for pediatric patients using either an allometric scaling or linear BSA model. Both models predict that, for a given artesunate dose in mg/kg of body weight, younger children are expected to have lower DHA exposure than older children or adults.

scholarly journals Evaluation of Pharmacokinetics and Pharmacodynamics of Deferasirox in Pediatric Patients

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1238
Author(s):  
Laura Galeotti ◽  
Francesco Ceccherini ◽  
Carmen Fucile ◽  
Valeria Marini ◽  
Antonello Di Paolo ◽  
...  
Keyword(s):  
High Performance ◽  
Pediatric Patients ◽  
Plasma Concentrations ◽  
High Performance Liquid Chromatographic ◽  
Volume Of Distribution ◽  
P Value ◽  
Population Pharmacokinetic ◽  
Threshold Values ◽  
Hematopoietic Stem ◽  
Abdominal Magnetic Resonance Imaging

Background: Deferasirox (DFX) is commonly used to reduce the chronic iron overload (IO) in pediatric patients. However, the drug is characterized by a large pharmacokinetic variability and approximately 10% of patients may discontinue the treatment due to toxicities. Therefore, the present retrospective study investigated possible correlations between DFX pharmacokinetics and drug-associated toxicities in 39 children (26 males), aged 2–17 years, who underwent an allogeneic hematopoietic stem cell transplantation. Methods: IO was diagnosed by an abdominal magnetic resonance imaging and DFX was started at a median dose of 500 mg/day. DFX plasma concentrations were measured by a high performance liquid chromatographic method with UV detection and they were analysed by nonlinear mixed-effects modeling. Results: The pharmacometric analysis demonstrated that DFX pharmacokinetics were significantly influenced by lean body mass (bioavailability and absorption constant), body weight (volume of distribution), alanine and aspartate transaminases, direct bilirubin, and serum creatinine (clearance). Predicted DFX minimum plasma concentrations (Ctrough) accounted for 32.4 ± 23.2 mg/L (mean ± SD), and they were significantly correlated with hepatic/renal and hematological toxicities (p-value < 0.0001, T-test and Fisher’s exact tests) when Ctrough threshold values of 7.0 and 11.5 mg/L were chosen, respectively. Conclusions: The population pharmacokinetic model described the interindividual variability and identified Ctrough threshold values that were predictive of hepatic/renal and hematological toxicities associated with DFX.

scholarly journals Methylprednisolone Plasma Concentrations During Cardiac Surgery With Cardiopulmonary Bypass in Pediatric Patients

2021 ◽  
Vol 8 ◽  
Author(s):  
Annewil van Saet ◽  
Gerdien A. Zeilmaker-Roest ◽  
Kevin M. Veen ◽  
Saskia N. de Wildt ◽  
Fritz Sorgel ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
Pediatric Patients ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Steep Slope ◽  
Time Curve ◽  
Linear Mixed Effects ◽  
Mixed Effects Modeling ◽  
Liquid Chromatography Tandem Mass

Introduction: To our knowledge, methylprednisolone pharmacokinetics and plasma concentrations have not been comprehensively investigated in children with congenital heart disease undergoing cardiac surgery with cardiopulmonary bypass. It is unknown whether there is a significant influence of cardiopulmonary bypass on the plasma concentrations of methylprednisolone and whether this may be an explanation for the limited reported efficacy of steroid administration in cardiac surgery with cardiopulmonary bypass.Methods: The study was registered in the Dutch Trial Register (NTR3579; https://www.trialregister.nl/trial/3428). Methylprednisolone 30 mg/kg was administered as an intravenous bolus after induction of anesthesia. Methylprednisolone concentration was measured with liquid chromatography tandem mass spectrometry and analyzed using linear mixed-effects modeling.Results: Thirty-nine patients were included in the study, of which three were excluded. There was an acute decrease in observed methylprednisolone plasma concentration on initiation of cardiopulmonary bypass (median = 26.8%, range = 13.9–48.14%, p &lt; 0.001). We found a lower intercept (p = 0.02), as well as a less steep slope of the model predicted methylprednisolone concentration vs. time curve for neonates (p = 0.048). A lower intercept (p = 0.01) and a less steep slope (p = 0.0024) if the volume of cell saver blood processed was larger than 91 ml/kg were also found.Discussion: We report similar methylprednisolone plasma concentrations as earlier studies performed in children undergoing cardiopulmonary bypass, and we confirmed the large interindividual variability in achieved methylprednisolone plasma concentrations with weight-based methylprednisolone administration. A larger volume of distribution and a lower clearance of methylprednisolone for neonates were suggested. The half-life of methylprednisolone in our study was calculated to be longer than 6 h for neonates, 4.7 h for infants, 3.6 h for preschool children and 4.7 h for school children. The possible influence of treatment of pulmonary hypertension with sildenafil and temperature needs to be investigated further.

scholarly journals Influence of maturation and growth on cefetamet pivoxil pharmacokinetics: rational dosing for infants.

1996 ◽  
Vol 40 (3) ◽  
pp. 567-574 ◽  
Author(s):  
W L Hayton ◽  
J Kneer ◽  
R de Groot ◽  
K Stoeckel
Keyword(s):  
Body Weight ◽  
Half Life ◽  
Pediatric Patients ◽  
Volume Of Distribution ◽  
Systemic Clearance ◽  
Older Children ◽  
Dosing Regimen ◽  
Urinary Recovery ◽  
The Mean ◽  
Plasma Half Life

The pharmacokinetics of intravenous (i.v.) cefetamet and the bioavailability of oral cefetamet pivoxil in infants aged 3.5 to 17.3 months who were hospitalized for urological surgery were characterized. The absorption of cefetamet pivoxil administered in a syrup formulation was 38 +/- 19% (n = 5) for infants, which was comparable to values observed for children and adults. The plasma half-life of i.v. cefetamet was 3.03 +/- 0.96 h (mean +/- standard deviation; n = 20) in the infants. This was not different from the value observed for normal adult subjects but was longer than that reported for children aged 3 to 12 years. Urinary recovery of cefetamet after i.v. administration to infants was 63.4 +/- 17.7% (n = 16), which was less than the 80% recovery found in older children and adults. The steady-state volume of distribution was 399 +/- 116 ml/kg of body weight. It was comparable in size and showed the same dependence on body weight as it did in children and adults. The mean systemic clearance per kilogram of body weight in the infants was lower than that in children and adults, apparently because of immaturity of clearance processes. A model that accounted for maturation and growth with increasing age was developed for the clearance. On the basis of this model, the clearance capacity increased from birth to 5 years by a factor of 4.5 because of maturation. Maturation progressed exponentially, with a half-life of 14 months. This model was used to develop dosing regimen guidelines for pediatric patients aged 3.5 months and older.

scholarly journals Endoscopic retrograde cholangiopancreatography in infants and children

2021 ◽  
Vol 09 (03) ◽  
pp. E292-E296
Author(s):  
Tone Lise Åvitsland ◽  
Lars Aabakken
Keyword(s):  
Endoscopic Retrograde Cholangiopancreatography ◽  
Medical Records ◽  
Pediatric Patients ◽  
Biliary Stricture ◽  
Infants And Children ◽  
University Hospital ◽  
Older Children ◽  
Endoscopic Retrograde ◽  
Procedure Codes ◽  
In Infants And Children

Abstract Background and study aims Previous reports have suggested that endoscopic retrograde cholangiopancreatography (ERCP) in pediatric patients are safe. However, the total number of cases presented in the literature remains small. We present results regarding safety and outcomes in pediatric patients undergoing ERCP at Oslo University Hospital. Patients and methods Patients < 18 years who underwent ERCP between April 1999 and November 2017 were identified using procedure codes. Medical records were examined for age, gender, diagnosis, indications, type of sedation, findings, interventions, and complications. Results A total of 244 procedures were performed in 158 patients. Fifty-six of these were in 53 infants (age ≤ 1 year). Mean age was 8.8 years. The youngest patient was 8 days old. Mean weight was 5.0 kg in infants, the smallest weighing 2.9 kg. Cannulation failed in 19 (7.8 %). The main indication in infants was suspicion of biliary atresia (n = 38). Six of the procedures (10.7 %) were therapeutic. In children the main indications were biliary stricture (n = 64) and investigation of primary sclerosing cholangitis (PSC) (n = 45). 119 (63.2 %) of these procedures were therapeutic.Complications were uncommon in infants; only two episodes of infection were registered. In children (> 1 year) post-ERCP pancreatitis were seen in 10.4 %. Conclusions Our retrospective series of ERCP procedures includes 56 procedures in infants, which is one of the largest series presented. Complications in infants are rare and post-ERCP pancreatitis was not seen. In older children 10.4 % experienced post-ERCP pancreatitis. In expert hands, ERCP was shown to be acceptably feasible and safe in infants and children.

scholarly journals The intravenous pharmacokinetics of diminazene in healthy dogs

2009 ◽  
Vol 80 (4) ◽  
Author(s):  
V. Naidoo ◽  
M.S.G. Mulders ◽  
G.E. Swan
Keyword(s):  
Plasma Concentrations ◽  
Compartmental Analysis ◽  
Central Compartment ◽  
Volume Of Distribution ◽  
Time Profile ◽  
Secondary Peak ◽  
German Shepherd ◽  
Plasma Pharmacokinetics ◽  
Healthy Dogs ◽  
Over 40 Years

Diminazene remains one of South Africa's most commonly used antiprotozoal agents for the management of babesiosis in dogs . Although the drug has been on the market for over 40 years, its intravenous pharmacokinetics are poorly known. To better understand the pharmacokinetics of the drug Berenil®, it was reconstituted in sterile water and administered intravenously to 6 adult German shepherd dogs. All 6 dogs demonstrated the previously described secondary peak in the plasma concentration versus time profile. The plasma pharmacokinetics for diminazene are described by both non-compartmental and compartmental models. From non-compartmental analysis, the area under curve to the last sample point (AUClast), clearance (CL) and volume of distribution (Vz) were 4.65±1.95 ng/mℓ/h, 0.77±0.18 ℓ/kg/h and 2.28±0.60 ℓ/kg, respectively. For compartmental modelling, the plasma concentrations were fitted to both a 2-compartmental open model and a recirculatory enterohepatic model. From the recirculation model, the rate of release and re-entry into the central compartment varied markedly with the rate of release from the gall bladder (Ttom) being estimated at 27 ± 20.90 h. Once released, drug re-entry into the central compartment was variable at 9.70±5.48 h. With normal biliary excretion time being about 2 h, this indicates that the redistribution cannot be occurring physiologically from the bile. Although it was not possible to identify the site from which sequestration and delayed release is occurring, it is believed that it is most likely from the liver. The study therefore showed that the secondary peak described for the pharmacokinetics of intramuscular administered diminazene in the dog is not related to biphasic absorption.

scholarly journals Foreign Body Aspiration in Infants and Older Children: A Comparative Study

2019 ◽  
Vol 99 (1) ◽  
pp. 47-51 ◽  
Author(s):  
Shorook Na’ara ◽  
Igor Vainer ◽  
Moran Amit ◽  
Arie Gordin
Keyword(s):  
Foreign Body ◽  
Medical Center ◽  
Age Groups ◽  
Signs And Symptoms ◽  
Foreign Body Aspiration ◽  
Preschool Age ◽  
Small Airways ◽  
Older Children ◽  
X Ray ◽  
Young Infants

Background: Foreign body aspiration (FBA) is a major cause of morbidity and mortality in children. It is a preventable event that predominates in preschool age. The signs and symptoms mimic respiratory diseases common in the same age-group. We compared FBA in infants to FBA in older children. Methods: Retrospective analysis of all the cases of suspected FBA of children under the age of 18 years hospitalized at one medical center during 2002 to 2016. We analyzed the data according to age: up to 1 year (infants) and 1 to 18 years. Results: One hundred seventy-five children with suspected FBA were admitted; of whom, 27 (15%) were infants and 148 (85%) were older children (age 1-18 years). For the 2 age groups, adults witnessed 85% and 73%, respectively, of the incidents ( P = .4). In the neonate group, 48% presented with normal X-ray findings compared to only 20% in the older group; 15% of the older group had a positive chest X-ray for a foreign body, while none had such in the infants’ group ( P = .01). For the 2 age groups, the majority of the FBs found were from organic origin. About half of the patients were diagnosed and managed within 24 hours of the aspiration event. In 10%, repeated bronchoscopy was performed due to a retained FB remnant. In a multivariate analysis, signs and symptoms ( P < .05), location of the FB ( P < .001), and witnessed aspiration ( P < .001) were independent prognostic factors for the length of hospitalization. Conclusion: Foreign body aspiration is not uncommon in young infants; the management is challenging due to small airways, the need to use smaller bronchoscopes, and the lack of working channel forces in pediatric bronchoscopes.

scholarly journals Pharmacokinetics of Once Daily Intraperitoneal Cefazolin in Continuous Ambulatory Peritoneal Dialysis Patients

2000 ◽  
Vol 11 (6) ◽  
pp. 1117-1121
Author(s):  
CHAI LUAN LOW ◽  
KAMANI GOPALAKRISHNA ◽  
WAI CHOONG LYE
Keyword(s):  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Half Life ◽  
Volume Of Distribution ◽  
Hplc Method ◽  
Dialysis Patients ◽  
Suitable Alternative ◽  
Once Daily ◽  
Cefazolin Sodium ◽  
Plasma Half Life

Abstract. This study determined the pharmacokinetic characteristics of once daily intraperitoneal (IP) cefazolin in continuous ambulatory peritoneal dialysis (CAPD) patients. Each of the 10 volunteer CAPD patients without active peritonitis received a single IP dose of 1 g of cefazolin sodium for a 6-h dwell. All patients underwent a fixed CAPD regimen comprising a first 6-h dwell followed by two 3-h dwells and a final 12-h overnight dwell. Blood and dialysate samples were collected at 0, 0.5, 1, 2, 3, 6 (end of first dwell), and 24 h after the administration of IP cefazolin. Any urine produced was collected over the 24-h study period. A validated HPLC method was used to analyze cefazolin in plasma, dialysate, and urine. The bioavailability was found to be 77.9 ± 3.1%, volume of distribution 0.20 ± 0.05 L/kg, and plasma half-life 39.9 ± 25.4 h. Mean total, renal, and peritoneal clearances were 4.5 ± 2.3, 1.4 ± 1.1, and 3.5 ± 1.8 ml/min, respectively. Mean plasma and dialysate concentrations at 24 h were 42.8 ± 14.3 and 31.8 ± 11.7 mcg/ml, respectively, well above the minimum inhibitory concentrations (MIC) of susceptible organisms. A once daily IP cefazolin dose of 500 mg/L gave desirable pharmacokinetic attributes for use as a suitable alternative to vancomycin for empiric treatment of CAPD-associated peritonitis.

scholarly journals Methemoglobinemia Associated with Metoclopramide Therapy in a Neonate

2004 ◽  
Vol 9 (1) ◽  
pp. 49-54
Author(s):  
Kristine G. Palmer ◽  
Laura P. James
Keyword(s):  
Health Care ◽  
Gastroesophageal Reflux ◽  
Health Care Providers ◽  
Side Effect ◽  
Pediatric Patients ◽  
Care Providers ◽  
Young Infants ◽  
Age Appropriate ◽  
The U.S

With the removal of cisapride from the U.S. market, practitioners have increasingly used other medications, such as metoclopramide, to treat gastroesophageal reflux in pediatric patients. We describe the case of a neonate who developed methemoglobinemia after receiving metoclopramide at doses slightly above the recommended age-appropriate dosage. Health care providers should be aware of this potentially serious side effect in young infants who receive this medication.

scholarly journals Population Pharmacokinetics of Fluconazole in Young Infants

2008 ◽  
Vol 52 (11) ◽  
pp. 4043-4049 ◽  
Author(s):  
K. C. Wade ◽  
D. Wu ◽  
D. A. Kaufman ◽  
R. M. Ward ◽  
D. K. Benjamin ◽  
...  
Keyword(s):  
Fixed Effects ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Relative Standard Error ◽  
Data Set ◽  
Mixed Effect ◽  
Young Infants ◽  
Relative Standard ◽  
Population Pk ◽  
The Impact

ABSTRACT Fluconazole is being increasingly used to prevent and treat invasive candidiasis in neonates, yet dosing is largely empirical due to the lack of adequate pharmacokinetic (PK) data. We performed a multicenter population PK study of fluconazole in 23- to 40-week-gestation infants less than 120 days of age. We developed a population PK model using nonlinear mixed effect modeling (NONMEM) with the NONMEM algorithm. Covariate effects were predefined and evaluated based on estimation precision and clinical significance. We studied fluconazole PK in 55 infants who at enrollment had a median (range) weight of 1.02 (0.440 to 7.125) kg, a gestational age at birth (BGA) of 26 (23 to 40) weeks, and a postnatal age (PNA) of 2.3 (0.14 to 12.6) weeks. The final data set contained 357 samples; 217/357 (61%) were collected prospectively at prespecified time intervals, and 140/357 (39%) were scavenged from discarded clinical specimens. Fluconazole population PK was best described by a one-compartment model with covariates normalized to median values. The population mean clearance (CL) can be derived for this population by the equation CL (liter/h) equals 0.015 · (weight/1)0.75 · (BGA/26)1.739 · (PNA/2)0.237 · serum creatinine (SCRT)−4.896 (when SCRT is >1.0 mg/dl), and using a volume of distribution (V) (liter) of 1.024 · (weight/1). The relative standard error around the fixed effects point estimates ranged from 3 to 24%. CL doubles between birth and 28 days of age from 0.008 to 0.016 and from 0.010 to 0.022 liter/kg/h for typical 24- and 32-week-gestation infants, respectively. This population PK model of fluconazole discriminated the impact of BGA, PNA, and creatinine on drug CL. Our data suggest that dosing in young infants will require adjustment for BGA and PNA to achieve targeted systemic drug exposures.

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