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- Bergquist, Filip, 1970, et al.
(författare)
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Pharmacokinetics of Intravenously (DIZ101), Subcutaneously (DIZ102), and Intestinally (LCIG) Infused Levodopa in Advanced Parkinson Disease
- 2022
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 99:10
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives Intestinal levodopa/carbidopa gel infusion (LCIG) is superior to oral treatment in advanced Parkinson disease. The primary objective of this trial was to investigate whether continuous subcutaneous or intravenous infusion with a continuously buffered acidic levodopa/carbidopa solution yields steady-state plasma concentrations of levodopa that are equivalent in magnitude, and noninferior in variability, to those obtained with LCIG in patients with advanced Parkinson disease. Methods A concentrated acidic levodopa/carbidopa (8:1) solution buffered continuously and administered intravenously (DIZ101) or subcutaneously (DIZ102) was compared with an approved LCIG in a randomized, 3-period crossover, open-label, multicenter trial. Formulations were infused for 16 hours to patients with Parkinson disease who were using LCIG as their regular treatment. Patients were recruited from several university neurology clinics but came to the same phase I unit for treatment. Pharmacokinetic variables and safety including dermal tolerance are reported. The primary outcomes were bioequivalence and noninferior variability of DIZ101 and DIZ102 vs LCIG with respect to levodopa plasma concentrations. Results With dosing adjusted to estimated bioavailability, DIZ101 and DIZ102 produced levodopa plasma levels within standard bioequivalence limits compared with LCIG in the 18 participants who received all treatments. Although the levodopa bioavailability for DIZ102 was complete, it was 80% for LCIG. Therapeutic concentrations of levodopa were reached as quickly with subcutaneous administration of DIZ102 as with LCIG and remained stable throughout the infusions. Owing to poor uptake of LCIG, carbidopa levels in plasma were higher with DIZ101 and DIZ102 than with the former. All individuals receiving any of the treatments (n = 20) were included in the evaluation of safety and tolerability. Reactions at the infusion sites were mild and transient. Discussion It is feasible to rapidly achieve high and stable levodopa concentrations by means of continuous buffering of a subcutaneously administered acidic levodopa/carbidopa-containing solution.
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| 2. |
- Gravas, S, et al.
(författare)
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Seeking evidence that cell kill guided thermotherapy gives results not inferior to those of transurethral prostate resection: Results of a pooled analysis of 3 studies of feedback transurethral microwave thermotherapy
- 2005
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 1527-3792 .- 0022-5347. ; 174:3, s. 1002-1006
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: We compared ProstaLund Feedback Treatment(R) (PLFT(R)) to transurethral prostate resection (TURP) in terms of efficacy and safety in a pooled analysis of 3 clinical studies with 1-year followup. Materials and Methods: Overall raw data on 183 patients with PLFT(R) and 65 with TURP were pooled. All studies had identical inclusion criteria, and the efficacy and safety of the method were evaluated using the International Prostate Symptom Score, maximum urine flow (Qmax), responder rate, bother score, prostate volume reduction and adverse events. Results: The response rate was 85.3% and 85.9% in the PLFT(R) and TURP groups, respectively. One-sided 95% CI analysis showed the noninferiority of PLFT(R) vs TURP for this variable. Mean International Prostate Symptom Score was significantly decreased in the PLFT(R) and TURP groups after 12 months (from 20.9 to 6.4 and 20.7 to 7.1, respectively). The 1-sided upper 95% CI of PLFT(R) was within the noninferiority definition compared with that of TURP. The bother score decrease in the PLFT(R) and TURP groups was not significant different (70.9% and 64.0%, respectively). An increase in Qmax from 7.7 to 16.1 ml per second 12 months after PLFT(R) was noted, while the improvement in Qmax in the TURP group was higher (from 7.5 to 18.6 ml per second). The 1-sided lower 95% CI was close (0.76) but it did not attain the predetermined level of noninferiority (0.80). Mean transurethral ultrasound determined volume 12 months after PLFT(R) and TURP was reduced by 32.8% and 58.1%, respectively. A significant correlation between the transurethral ultrasound determined prostate volume reduction and estimated cell kill was found (r = 0.456, p <0.000001). Serious adverse events with causality occurred in 15.4% of patients with TURP compared with 6.0% in those with PLFT(R) (p = 0.035). Conclusions: Combined experience from our pooled analysis indicates that PLFT(R) challenges TURP in terms of efficacy and safety after 1 year of followup.
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| 3. |
- Nyholm, Dag, et al.
(författare)
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Frequent administration of levodopa/carbidopa microtablets vs levodopa/carbidopa/entacapone in healthy volunteers
- 2013
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 127:2, s. 124-132
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES:An oral dispersible microtablet formulation of levodopa/carbidopa 5/1.25 mg (LC-5) was developed for individualized repeated dosing. The aim was to compare pharmacokinetic profiles of LC-5 and levodopa/carbidopa/entacapone (LCE).MATERIALS AND METHODS:A randomized, crossover study was carried out in 11 healthy subjects. Plasma concentrations of levodopa, carbidopa and 3-O-methyldopa were determined after intake of 300 mg levodopa during the day, either as three intakes of 100/25/200 mg LCE or as a morning dose of 75/18.25 mg followed by five repeated doses of 45/11.25 mg LC-5.RESULTS:Repeated dosing (2.4-hourly) with LC-5 microtablets compared to LCE (6-hourly) avoided long periods with low plasma levodopa levels. Time to maximum plasma concentrations was significantly shorter for LC-5. LC-5 showed lower fluctuation index (FI) in plasma compared to LCE (ANOVA P = 0.0028). FI for dose 2-5 was on average 1.26 for levodopa in LC-5, and 2.23 for dose 1-2 of LCE. The ratio between the two mean FI:s is 0.565; that is, LC-5 gave nearly half the FI as compared to LCE.CONCLUSIONS:Fractionation of levodopa with LC-5 into small, frequent administrations as compared to standard administrations of LCE decreased the FI in plasma for both levodopa and carbidopa by nearly half.
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