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P Brannan

Publications and source records attributed to P Brannan.

10 recordsLinked to original sources
PubMed2000

Reduced variability of neoral pharmacokinetic studies in pediatric renal transplantation.

In adult renal transplant recipients the Neoral area under the curve (AUC) displays less inter- and intra-individual variability than Sandimmune, and those renal transplant recipients with reduced intra-individual variability of the AUC have a lower risk for chronic rejection. As variability of Neoral pharmacokinetic (Pk) parameters has not been investigated in pediatric renal transplant recipients, we retrospectively analyzed 453 Pk profiles in 14 pediatric patients who were switched from Sandimmune to Neoral and compared the inter- and intra-individual variability of the Pk profiles on both formulations. After the switch, we observed less inter- and intra-individual variability of AUC, the 2-h concentration, and the oral clearance. As clearance with both formulations is supposedly equal, the significantly lower intra-individual variability of oral clearance is most likely an effect of less variable absorption. While the lower inter-individual variability of the Pk parameters suggests increased success in keeping cyclosporine concentrations on target, the lower intra-individual variability leads to the hypothesis that with Neoral, a lower incidence of chronic rejection might be achieved.

Adolescent↗
PubMed1999

A limited sampling strategy for the estimation of Neoral AUCs in pediatric patients.

The improved pharmacokinetics of Neoral allows the development of an accurate estimate of the full area under the concentration time curve (AUC) from a limited sampling strategy. As no such strategy has been derived from pharmacokinetic data obtained from children on 12-hourly dosing, and as patient convenience demands shorter sampling times, we derived a limited sampling strategy from 45 AUCs obtained from 19 pediatric renal transplant patients by stepwise forward multiple regression, and prospectively tested them on a separate group of 49 AUCs obtained from 18 pediatric renal transplant patients. Full cyclosporine (CsA) AUCs were obtained from samples drawn pre dose (C0) and at 2, 4, 6, 8 and 12 h post dose (C2, C4, C6, C8, and C12). High-precision predictions of full AUC were obtained based on the formula: AUC = 444 + 3.69 x C0 + 1.77 x C2 + 4. 1 x C4 (mean prediction error +/- SD = 0.3 +/- 6.4%, 95% confidence interval=-1.7% to 1.9%.) In conclusion, CsA exposure in pediatric renal transplant patients on 12-hourly Neoral dosing can be reliably predicted by an early time point-based limited sampling strategy in children. This formula has the advantage of obtaining trough as well as AUC from one brief, convenient sampling period.

Adolescent↗
PubMed1998

A limited sampling strategy for the estimation of eight-hour neoral areas under the curve in renal transplantation.

Neoral, the microemulsion formulation of cyclosporine (CsA), demonstrates more consistent bioavailability than the corn oil formulation Sandimmune. Because of Neoral's rapid peak and metabolism, 8-hour dosing has to be used in many pediatric and some adult patients to maintain adequate CsA peak-to-trough ratios. Although the area under the curve (AUC) is considered the best estimate of total drug exposure, it requires repeated blood sampling. Abbreviated AUC profiles yielding excellent estimates of Neoral AUC with twice daily dosing have been described, but no such abbreviated strategy exists for 8-hour dosing. One hundred fifty-two pharmacokinetic profiles in 23 patients were used to derive and prospectively test a limited two-sample strategy to predict Neoral AUCs in pediatric and adult patients on 8-hour dosing regimens of Neoral. The formula was derived from 69 full 8-hour CsA pharmacokinetic profiles in nine children who underwent renal transplantation. Stepwise forward linear and multiple-curve regression techniques assessed the relative importance of single and combination concentration time points to predict AUC. The abbreviated profiles were validated by comparing the mean prediction error for each regression equation. The abbreviated profile calculated by second (C2)- and fourth (C4)-hour levels (AUC = 129 + 1.84 x C2 + 4.39 x C4) correlated well with the full AUC (r2 = 0.96; p < 0001). Mean prediction error was -0.4% +/- 5.48%, and no values fell outside the clinically acceptable 15% prediction error limit. Prospectively applying the formula to 83 AUCs of 14 adults who underwent renal transplantation and were taking Neoral three times a day demonstrated an excellent fit (r2 = 0.93; p < 0.001), with 94% of predicted values falling inside the +/-15% limit. The authors describe the development of a clinically acceptable, limited sampling strategy to predict 8-hour Neoral AUCs in children and adults who underwent renal transplantation.

Adolescent↗
PubMed1986

Selecting and educating perioperative nurses for an ambulatory surgery setting.

A decision was made that review of technical skills for the perioperative and postanesthesia nurses hired from within the hospital was not necessary because they all had experience in their specialty areas. Those hired from other areas of the hospital will spend one month with a preceptor in the postanesthesia care area, one month in our short stay unit with a preceptor, and one month either in class or OR observation. All will have formal classes on anesthesia, fluid and electrolytes, and the philosophy of ambulatory surgery. These employees were released from their previous positions three months before the projected opening date of the new unit to allow them to learn the new skills. The patient care manager assigned responsibilities to the perioperative nurses hired from the main OR. They were asked to research needed equipment and supplies for various procedures in the different specialty areas. The patient care manager felt this would help them make a smooth transition to the new unit by making them feel like members of the team. My original hypothesis that perioperative nurses will not only rise to the occasion, but will far exceed our expectations will be tested when we move to the new ambulatory surgery unit. Although our opening date has been delayed, I am confident that our forethought and preparation will result in a smooth transition and an efficient staff.

Humans↗
PubMed1976

Ion transport changes during calcitonin-induced intestinal secretion in man.

Previous studies have shown that synthetic salmon calcitonin (SCT) infused intravenously causes secretion of water and electrolytes in the jejunum of normal human subjects. The present experiments were carried out to learn more about the nature of this intestinal secretory process. During SCT- or synthetic human calcitonin (HCT)-induced intestinal secretion, the following observations were made: (1) There was no change in potential difference; (2) Cl was secreted against an electrochemical gradient; (3) unidirectional Na flux out of the lumen was decreased while the opposite flux was normal; (4) luminal pCO2 fell; (5) addition of glucose to the jejunal contents stimulated Na abdsorption, and this in turn counteracted the secretory effect of calcitonin. These findings suggest that calcitonin induces active Cl secretion and inhibits active Na absorption, and that HCO3 absorption is reduced by virtue of OH secretion; furthermore, jejunal glucose absorption and glucose-stimulated Na absorption are intact during calcitonin-induced secretion. Intravenous infusion of HCT caused intestinal secretion only when blood levels were much higher than occur physiologically; therefore, calcitonin is probably not a mediator of spontaneous variations of intestinal transport in normal people. However, because calcitonin induces secretion in the ileum as well as in the jejunum, hypercalcitonemia (within the range commonly found in patients with medullary carcinoma of the thyroid) could be a cause of severe secretory diarrhea.

Action Potentials↗