EPS3.10 Clinical pharmacokinetics and dose recommendations for posaconazole gastro-resistant tablets in children with cystic fibrosis

This study was performed to determine the clinical pharmacokinetics of tobramycin in six patients with cystic fibrosis (CF) after inhalation of 600 mg. Tobramycin was administered with an ultrasonic nebulizer (WISTO SENIOR). Blood and urine were sampled until 24 h after inhalation. Maximum tobramycin levels in serum varied from 0.19 to 2.57 mg/liter (mean 1.27 mg/liter; standard deviation, 1.07 mg/liter). Systemic availability (calculated from urinary output) ranged from 6.0 to 27.4% (mean, 17.5%; standard deviation, 8.8%). The results illustrate that, provided that the systemic availability of tobramycin is a reflection of pulmonary deposition, inhalation studies with CF patients should have a concentration-controlled design. Furthermore, reliance on dose recommendations from the literature for a new patient starting on this treatment is not justified, but it is mandatory that deposition kinetics be studied for each patient and for each nebulizer. It may well be that, with higher levels of deposition, dosages lower than those recommended in the literature will suffice to obtain the desired clinical effect. In addition, the reverse may also be the case.

Download Full-text

Clinical Pharmacokinetics and Dose Recommendations for Posaconazole in Infants and Children

Clinical Pharmacokinetics ◽

10.1007/s40262-018-0658-1 ◽

2018 ◽

Vol 58 (1) ◽

pp. 53-61 ◽

Cited By ~ 6

Author(s):

Sophida Boonsathorn ◽

Iek Cheng ◽

Frank Kloprogge ◽

Carlos Alonso ◽

Charmion Lee ◽

...

Keyword(s):

Infants And Children ◽

Clinical Pharmacokinetics ◽

Dose Recommendations ◽

In Infants And Children

Download Full-text

Evaluating the Impact of Education on Pharmacist Tobramycin Dose Recommendations for Cystic Fibrosis and a Review of Perceptions on Pharmacist-Led Charting

Journal of Pharmacy Practice ◽

10.1177/08971900211018419 ◽

2021 ◽

pp. 089719002110184

Author(s):

Tran Le ◽

Louise Lord ◽

Silvana Pignataro ◽

Diana Simioni ◽

Ron Cheah

Keyword(s):

Cystic Fibrosis ◽

Educational Intervention ◽

Therapeutic Drug ◽

Median Score ◽

Medical Doctors ◽

Cross Sectional Survey ◽

Retrospective Audit ◽

Dose Recommendations ◽

The Impact ◽

Case Based

Background: Pharmacists routinely interpret and optimize tobramycin dosing for people with cystic fibrosis (PwCF). Objectives: To determine the impact of tobramycin therapeutic drug monitoring (TDM) education on pharmacist dose recommendations, and to explore nurses’ and medical doctors’ perceptions toward pharmacist-led TDM charting. Methods: This study involved 3 phases: a 12-month retrospective audit of PwCF prescribed tobramycin to identify the appropriateness of pharmacists’ dose recommendations, a pharmacist tobramycin educational intervention utilizing a voiceover presentation with pre- and post-online tobramycin TDM assessment (involving multiple choice pharmacokinetics and case-based scenario questions), and a cross-sectional survey of respiratory nurses’ and doctors’ perceptions toward pharmacist-led TDM charting. The pharmacists’ dose recommendations, in the audit and case-based questions, were considered appropriate if subsequent levels achieved the targeted area under the curve (AUC). Results: Audit results revealed that 44.4% of the 277 pharmacist dose recommendations identified were appropriate. The pre- and post-interventional assessments were completed by 51 and 52 pharmacists, respectively. Post intervention, correct scores were significantly higher than pre-intervention, evident in both the pharmacokinetics (median score 75% vs 100%; P = 0.048) and case-based scenario (median score 60% vs 90%; P < 0.0001) questions. Of the 54 nurses and medical doctors surveyed, 92.6% supported the implementation of pharmacist-led tobramycin charting. Conclusion: The study demonstrated an increased accuracy and appropriateness of pharmacists’ tobramycin pharmacokinetics knowledge and TDM dose recommendations post-educational intervention and highlighted nurses’ and medical doctors’ support of pharmacist-led tobramycin TDM charting.

Download Full-text

Clinical pharmacokinetics and dose recommendations for posaconazole gastroresistant tablets in children with cystic fibrosis

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkab312 ◽

2021 ◽

Author(s):

Siân Bentley ◽

Jane C Davies ◽

Silke Gastine ◽

Jackie Donovan ◽

Joseph F Standing

Keyword(s):

Cystic Fibrosis ◽

Model Building ◽

Compartment Model ◽

Individual Variability ◽

Therapeutic Drug ◽

Population Pharmacokinetic ◽

Electronic Patient Records ◽

Clinical Pharmacokinetics ◽

Dose Scheme ◽

Highly Correlated

Abstract Objectives To investigate the population pharmacokinetics of posaconazole gastroresistant tablets in children with cystic fibrosis (CF) and perform simulations to recommend optimal doses. Patients and methods Children from a paediatric CF centre who had received posaconazole tablets and underwent therapeutic drug monitoring were identified from pharmacy records. Relevant clinical data were collated from case notes and electronic patient records and used to develop an allometrically scaled population pharmacokinetic model. A stepwise covariate model-building exercise evaluated the influence of interacting medicines and liver function. Results One hundred posaconazole serum concentrations were collected from 37 children with a median age of 14 years (range 7–17). Posaconazole pharmacokinetics were adequately described by a one-compartment model with inter-individual variability on clearance. Dose simulations demonstrated a 77%–83% probability of attaining a trough target of 1 mg/L with a dose of 300 mg every 12 h for two doses then 300 mg once daily (OD) in children aged 6–11 years; and 86%–88% with a dose of 400 mg every 12 h for two doses then 400 mg OD in adolescents aged 12–17 years. This dose scheme also yielded a 90% probability of achieving an AUC of 30 mg·h/L. AUC and trough concentration were highly correlated (r2 = 0.98). Simulations showed that trough concentrations of >0.75 mg/L would exceed an AUC of 30 mg·h/L in 90% of patients. Conclusions A starting dose of 300 mg OD in those aged 6–11 years and 400 mg OD in those aged 12–17 years (following loading doses) yields a 90% probability of attaining an AUC of 30 mg·h/L.

Download Full-text

Correction to: Clinical Pharmacokinetics and Dose Recommendations for Posaconazole in Infants and Children

Clinical Pharmacokinetics ◽

10.1007/s40262-018-0722-x ◽

2018 ◽

Vol 58 (1) ◽

pp. 141-141

Author(s):

Sophida Boonsathorn ◽

Iek Cheng ◽

Frank Kloprogge ◽

Carlos Alonso ◽

Charmion Lee ◽

...

Keyword(s):

Infants And Children ◽

Clinical Pharmacokinetics ◽

Dose Recommendations ◽

In Infants And Children

Download Full-text

Pregnancy in cystic fibrosis of the pancreas

JAMA ◽

10.1001/jama.195.12.993 ◽

1966 ◽

Vol 195 (12) ◽

pp. 993-1000 ◽

Cited By ~ 9

Author(s):

R. J. Grand

Keyword(s):

Cystic Fibrosis

Download Full-text

Freeze-Fracture Examination of Tight Junctions of Human Eccrine Sweat Glands

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s1431927600002786 ◽

1980 ◽

Vol 38 ◽

pp. 634-635

Author(s):

J. V. Briggman ◽

J. Bigelow ◽

H. Bank ◽

S. S. Spicer

Keyword(s):

Cystic Fibrosis ◽

Freeze Fracture ◽

Sweat Glands ◽

Hypertonic Solution ◽

Dark Cells ◽

Clear Cells ◽

Junctional Complexes ◽

Secretory Coil ◽

Eccrine Sweat Glands ◽

Eccrine Sweat

The prevalence of strands shown by freeze-fracture in the zonula occludens of junctional complexes is thought to correspond closely with the transepi-thelial electrical resistance and with the tightness of the junction and its obstruction to paracellular flow.1 The complexity of the network of junc¬tional complex strands does not appear invariably related to the degree of tightness of the junction, however, as rabbit ileal junctions have a complex network of strands and are permeable to lanthanum. In human eccrine sweat glands the extent of paracellular relative to transcellular flow remains unknown, both for secretion of the isotonic precursor fluid by the coil and for resorption of a hypertonic solution by the duct. The studies reported here undertook, therefore, to determine with the freeze-fracture technique the complexity of the network of ridges in the junctional complexes between cells in the secretory coil and the sweat ducts. Glands from a patient with cystic fibrosis were also examined because an alteration in junctional strands could underlie the decreased Na+ resorption by sweat ducts in this disease. Freeze-fracture replicas were prepared by standard procedures on isolated coil and duct segments of human sweat glands. Junctional complexes between clear cells, between dark cells and between clear and dark cells on the main lumen, and between clear cells on intercellular canaliculi of the coil con¬tained abundant anastomosing closely spaced strands averaging 6.4 + 0.7 (mean + SE) and 9.0 +0.5 (Fig. 1) per complex, respectively. Thus, the junctions in the intercellular canaliculi of the coil appeared comparable in complexity to those of tight epithlia. Occasional junctions exhibited, in addition, 2 to 5 widely spaced anastomosing strands in a very close network basal to the compact network. The fewer junctional complexes observed thus far between the superficial duct cells consisted on the average of 6 strands arranged in a close network and 1 to 4 underlying strands that lay widely separated from one another (Fig. 2). The duct epitelium would, thus, be judged slightly more "leaky" than the coil. Infrequent junctional complexes observed to date in the secretory coil segment of a cystic fibrosis specimen disclosed rela¬tively few closely crowded strands.

Download Full-text