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Books: 0	Journals: 2	Articles: 3

Originals

Pediatric IgA nephropathy: clinical features at presentation and outcome for African-Americans and Caucasians

K.K. Lau, L.W. Gaber, N.M. Delos Santos, K.A. Fisher, S.J. Grimes and R.J. Wyat

Volume 62 (2004) p. 167 - 172

Abstract

K.K. Lau, L.W. Gaber, N.M. Delos Santos, K.A. Fisher, S.J. Grimes and R.J. Wyat

¹Children’s Foundation Research Center at the Le Bonheur Children’s Medical Center, Departments of ²Pediatrics and ³Pathology, University of Tennessee Health Science Center, Memphis, TN, USA
Aim: To determine the disease severity at onset and outcome for African-American and Caucasian pediatric patients with IgA nephropathy diagnosed at the Le Bonheur Children’s Medical Center since 1990. Design/Methods: The study population included all patients diagnosed with IgA nephropathy at the Le Bonheur Children’s Medical Center from January 1990 through February 2004. All were below age 18 at biopsy. Clinical features assessed at diagnosis were age, gender, presence of hypertension, history of macroscopic hematuria, degree of proteinuria, severity of renal histology and pattern for immunofluorescent reactants. Statistics: Student’s t-test was used to compare age at biopsy and length of follow-up between the 2 groups. Fisher’s exact test was used to compare features at presentation and patterns of immunofluorescence. Kidney survival was predicted by the Kaplan-Meier method. Results: Forty-seven patients (17 African-American, 29 Caucasian) were studied. Clinical features at diagnosis and pattern for all immunofluorescent reactants did not differ significantly between the 2 groups. Mesangial deposition of C1q occurred in 4/17 African-Americans as compared to 1/27 Caucasians (p = 0.06). Four patients (2 African-Americans, 2 Caucasians) progressed to end-stage renal disease. Predicted kidney survival was 96% (94% in African-Americans and 97% in Caucasians) at 1 year and 91% (94% in African-Americans and 89% in Caucasians) at 5 years from diagnosis. Mean time from diagnosis to end-stage renal disease or last follow-up was 3.3 years (3.8 for African-Americans, 3.0 for Caucasians). Macroscopic hematuria occurred prior to diagnosis for 90% of the Caucasian as compared to 61% of the African-American patients (p = 0.03). Urinalysis was normal at last follow-up visit for 24% of African-American patients and 32% of Caucasian patients. Conclusion: In a relatively small sample from a single center, except for the difference in macroscopic hematuria, clinical features at diagnosis and outcome of IgA nephropathy appear similar for African-American and Caucasian pediatric patients.Correspondence to:
Dr. R.J. Wyatt
Division of Pediatric Nephrology
Room 301 West Patient Tower
Children’s Foundation Research Center
50 N. Dunlap
Memphis, TN 38103, USA
Email: [email protected]

Original Research

Pharmacokinetic comparisons of three nasal fentanyl formulations; pectin, chitosan and chitosan-poloxamer 188

A. Fisher, M. Watling, A. Smith and A. Knight

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Volume 48 p. 138 - 145

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 48 – No. 2/2010 (138-145)

Pharmacokinetic comparisons of three nasal fentanyl formulations; pectin, chitosan and chitosan-poloxamer 188

A. Fisher¹, M. Watling¹, A. Smith¹ and A. Knight²

¹Archimedes Development Limited, Albert Einstein Centre, Nottingham Science and Technology Park, University Boulevard, Nottingham, and ²Evicom Limited, Somerset House, Teddington, UK
Objectives: To optimize the absorption profile and reduce C_max, three new fentanyl nasal spray formulations have been developed: fentanyl pectin (FPNS), fentanyl chitosan (FChNS) and fentanyl in chitosan-poloxamer 188 (FChPNS). The venous pharmacokinetic profiles and tolerability of these formulations were assessed and compared with oral transmucosal fentanyl citrate (OTFC) lozenge. Subjects and methods: This randomized, open-label, crossover study was conducted in opioid-naïve, healthy adult volunteers. Subjects were dosed under naltrexone blockade on four occasions with three nasal sprays (100 µg in 100 µl) and OTFC 200 µg. Fentanyl venous plasma concentrations were measured up to 24 h post-dose. Tolerability was assessed by clinical nasal assessments and a nasal reactogenicity questionnaire. Results: 18 subjects were enrolled and completed the study. The mean dose-normalized AUC_0-∞ for each nasal formulation was significantly higher (p < 0.05) compared with OTFC. Bioavailability compared with OTFC was significantly greater for all nasal fentanyl formulations (FPNS 132.4%, FChNS 154.1%, FChPNS 122.3%). Median t_max (FPNS 0.33 h, FChNS 0.17 h, FChPNS 0.26 h) were significantly (p < 0.001) reduced (OTFC 1.5 h) and mean C_max significantly increased with all nasal formulations compared with OTFC. Nasal reactogenicity symptom incidence was lowest for the FPNS formulation (FPNS 2, FChNS 28 and FChPNS 45). Conclusions: All nasal formulations demonstrated significantly increased systemic exposure and reduced times to peak plasma values compared with OTFC. The FPNS formulation exhibited the most favorable nasal and general tolerability profiles. It appears suitable for further investigation in breakthrough cancer pain management.Correspondence to:
A. Fisher, PhD
Archimedes Development Limited
Albert Einstein Center
Nottingham Science and Technology Park
University Boulevard
Nottingham, NG7 2TN, UK
Email: [email protected]

Bioavailability Section

Pharmacokinetics and relative bioavailability of fentanyl pectin nasal spray 100 – 800 µg in healthy volunteers

A. Fisher, M. Watling, A. Smith and A. Knight

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42.00 $

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42.00 $

Volume 48 p. 860 - 867

Abstract

International Journal of Clinical Pharmacology and Therapeutics, Vol. 48 – No. 12/2010 (860-867)

Pharmacokinetics and relative bioavailability of fentanyl pectin nasal spray 100 – 800 µg in healthy volunteers

A. Fisher¹, M. Watling¹, A. Smith¹ and A. Knight²

¹Archimedes Development Limited, Albert Einstein Centre, Nottingham Science and Technology Park, University Boulevard, Nottingham, and ²Evicom Limited, Somerset House, Teddington, UK
Objectives: Fentanyl pectin nasal spray (FPNS) is formulated as a solution utilizing PecSys^®; pectin based enabling technology (Archimedes). On contact with the nasal mucosa the formulation will gel and modulate fentanyl absorption while limiting nasal drip or runoff. This single-dose volunteer study compared the pharmacokinetics of FPNS 100, 200, 400, and 800 µg doses and assessed bioavailability relative to oral transmucosal fentanyl (OTFC) 200 µg. Safety and dose proportionality were also examined. Subjects and methods: 16, opioid-naïve subjects were dosed on five separate visits under naltrexone block. FPNS doses were administered using a Pfeiffer device delivering 100 µl. Devices were filled with either 1.57 mg/ml (100 and 200 µg dosing) or 6.28 mg/ml fentanyl citrate (400 and 800 µg). Venous blood samples were collected up to 48 h after dosing and plasma fentanyl concentrations measured. Results: Median t_max values for FPNS ranged from 15 to 21 min post-dose and were dose-independent. At 200 µg C_max values were 2.3-fold higher for FPNS compared with OTFC. Mean relative bioavailability of FPNS to OTFC ranged from 103% to 163%. Dose proportionality for C_max and AUC_0–1 across the FPNS range was statistically confirmed. Drug absorption also increased in a close to dose-proportional manner for AUC_0–inf. Conclusions: FPNS has a shorter t_max, higher C_max and greater bioavailability than OTFC and is well tolerated. The dose proportionality of Cmax and AUC_0–1 was demonstrated. It is concluded that the pharmacokinetic profile of FPNS suggests this product is suitable for clinical investigation in breakthrough pain in cancer patients.Correspondence to:
A. Fisher, PhD
Archimedes Development Limited
Albert Einstein Centre
Nottingham Science and Technology Park
University Boulevard, Nottingham, NG7 2TN, UK
Email: [email protected]

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