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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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.
Authors: Dongni Johansson; Anders Ericsson; Anders Johansson; Alexander Medvedev; Dag Nyholm; Fredrik Ohlsson; Marina Senek; Jack Spira; Ilias Thomas; Jerker Westin; Filip Bergquist Journal: CNS Neurosci Ther Date: 2018-01-25 Impact factor: 5.243
Authors: Dag Nyholm; Per Odin; Anders Johansson; Krai Chatamra; Charles Locke; Sandeep Dutta; Ahmed A Othman Journal: AAPS J Date: 2012-12-11 Impact factor: 4.009
Authors: Marina Senek; Sten-Magnus Aquilonius; Håkan Askmark; Filip Bergquist; Radu Constantinescu; Anders Ericsson; Sara Lycke; Alexander Medvedev; Mevludin Memedi; Fredrik Ohlsson; Jack Spira; Jerker Westin; Dag Nyholm Journal: Eur J Clin Pharmacol Date: 2017-01-18 Impact factor: 2.953