***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE : To compare the bioavailability of three generic br and s of carbamazepine tablets with that of a proprietary br and in adult patients with epilepsy . DESIGN : A double-blind , r and omized , three-phase crossover study . SETTING : A psychiatric facility . PARTICIPANTS : Eighteen patients with epilepsy who had taken carbamazepine at least 5 months before entering the study . MAIN OUTCOME MEASURES : Ten blood specimens from each patient were collected at steady-state . Plasma concentration of carbamazepine  was analyzed for pharmacokinetic parameters such as maximum plasma concentration ( Cmax ) , mean time to reach maximum concentration ( tmax ) , and mean AUC . RESULTS : There were no statistically significant differences in these parameters among four br and s of carbamazepine . However , when comparing the 90 % CI of AUC of three generic br and s with that of the proprietary br and , the AUC of two generic br and s lay within a range of 80 % to 120 % . The effects of gender and each br and of carbamazepine on these pharmacokinetic parameters were also analyzed . Breakthrough seizures occurred even though the plasma concentration of carbamazepine was therapeutic . CONCLUSIONS : The bioavailability of two generic br and s of carbamazepine tablets ( Carmapine and Carzepine ) and the proprietary br and ( Tegretol ) were equivalent in this sample of adult patients with epilepsy BACKGROUND Lamotrigine is an antiepileptic drug which has been used in the treatment of epilepsy and bipolar disorder . A search of the literature did not find previously published bioequivalence and pharmacokinetic evaluations of lamotrigine in healthy Thai male volunteers . OBJECTIVE The aim of this study was to compare the pharmacokinetic parameters between 2 br and s of lamotrigine in healthy Thai male volunteers . METHODS A r and omized , single-dose , 2-period , 2-sequence , crossover study design with a 2-week washout period was conducted in healthy Thai males . Subjects were r and omized to receive either the test or reference formulation in the first period . All subjects were required to be nonsmokers and without a history of alcohol or drug abuse . Plasma sample s were collected over a 120-hour period after 100-mg lamotrigine administration in each period . A vali date d high-performance liquid chromatography ultraviolet method was used to analyze lamotrigine concentration in plasma . Pharmacokinetic parameters were determined using a noncompartmental method . Bioequivalence between the test and reference products , as defined by the US Food and Drug Administration ( FDA ) , is determined when the ratio for the 90 % CIs of the difference in the means of the log-transformed AUC(0-t ) , AUC(0-infinity ) , and C(max ) of the 2 products are within 0.80 and 1.25 . Adverse events were determined by measuring vital signs after dosing . Subjects were also asked if they suffered from undesirable effects such as nausea , vomiting , dizziness , and headache . RESULTS This bioequivalence study was performed in 24 healthy Thai males ( mean [ SD ] age , 20.5 [ 1.3 ] years ; range , 19 - 24 years ; weight , 62.5 [ 7.4 ] kg ; height , 172.8 [ 6.9 ] cm ; body mass index , 20.9 [ 2.0 ] kg/m(2 ) ) . The mean ( SD ) C(max ) and T(max ) of the test formulation of lamotrigine were 1.7 ( 0.3 ) microg/mL and 1.2 ( 0.9 ) hours , respectively . The mean ( SD ) C(max ) and T(max ) of the reference formulation of lamotrigine were 1.7 ( 0.3 ) microg/mL and 1.4 ( 1.0 ) hours , respectively . The mean ( SD ) AUC(0-t ) was 67.1 ( 13.2 ) microg/mL x h(-1 ) for the test product and 66.4 ( 14.6 ) microg/mL x h(-1 ) for the reference product . The mean ( SD ) AUC(0-infinity ) was 74.9 ( 18.3 ) microg/mL x h(-1 ) for the test product and 74.3 ( 20.5 ) microg/mL x h(-1 ) for the reference product . The mean ( SD ) t((1/2 ) ) values were 35.0 ( 7.6 ) hours for the test product and 34.7 ( 7.6 ) hours for the reference product . The mean test/reference ratios for AUC(0-t ) , AUC(0-infinity ) , and Cmax were 1.01 , 1.01 , and 1.05 , respectively . The parametric 90 % CIs for AUC(0-t ) , AUC(0-infinity ) , and Cmax were 0.98 to 1.05 , 0.98 to 1.06 , and 0.98 to 1.13 , respectively . Following administration , dizziness or headache was reported in 2 subjects in the test group and 1 subject in the reference group . CONCLUSION The results of this study suggest that the test product was bioequivalent to the reference product in these healthy Thai male subjects , based on the US FDA 's regulatory definition Objective : In this study our aim was to assess pharmacokinetic effects and adverse cognitive effects of switches between generic and br and ed formulations of carbamazepine ( CBZ ) . Method : Twelve patients were included in a r and omized open-label , observer-blind , cross-over design with a double-baseline period , comparing three different formulations of carbamazepine in monotherapy – the innovatory br and ed form Tegretol and two generic forms , CBZ Pharmachemie and CBZ Pharbita .  Cognitive assessment was carried out at baseline and 3 days after a cross-over . Results : Area under the curve and a number of pharmacokinetic properties ( serum concentration day curves , change in serum concentration ( delta scores ) , peak/trough concentrations and peak time ) did not differ among the three CBZ formulations . Therefore , the basic assumption for this study , i.e. to test pharmacokinetic-related differences in cognitive profile , was not met . In line with these findings , none of the cognitive variables showed statistically significant differences with respect to the cognitive profile during the day . Conclusion : Switches between the investigated generic CBZ formulations and the br and ed product did not result in any difference in cognitive profiles . These results are not necessarily valid , though , for other generic forms of CBZ , for other types of antiepileptic drugs or for CBZ treatment in higher doses or in polytherapy OBJECTIVE To assess the bioavailability of carbamazepine from two br and s of carbamazepine -- Tegretol 200 and Zen-200 . METHODS A two-way r and omised cross-over bioavailability of carbamazepine was carried out in twelve healthy male volunteers . Coded plasma sample s were analysed for levels of carbamazepine by high performance liquid chromatography ( HPLC ) method . Tegretol 200 and Zen-200 were tested for in-vitro dissolution profiles . RESULTS The mean Cmax , Tmax and t1/2a for Tegretol 200 were : 2.17 + /- 0.42 mcg/mL , 11.67 + /- 6.37 h and 2.72 + /- 1.87 h ; for Zen-200 were 3.10 + /- 0.05 mcg/mL , 3.50 + /- 2.11 h and 0.76 + /- 0.76 h respectively . These values were statistically significant . However AUC ( 0 - 96 h ) value of 150.16 + /- 27.13 mcg/ml.h after Zen-200 was not statistically significant as compared to 128.68 + /- 20.22 mcg/ml.h after Tegretol 200 . The in-vitro dissolution profiles of the two formulations were dissimilar . The fluctuations in CBZ levels after Tegretol 200 was significantly less as compared to Zen-200 . The absorption profile as judged by parameter ' A ' was 50.44 + /- 10.95 for Tegretol 200 and 42.49 + /- 18.89 for Zen-200 . CONCLUSION Based on parameter ' A ' and other pharmacokinetic parameters , the marketed generic carbamazepine product , Zen-200 is not bioequivalent to Tegretol 200 We performed a r and omized double-blind crossover therapeutic bioequivalency study of a generic ( Epitol ) versus a br and name ( Tegretol ) carbamazepine product under steady-state conditions in 40 epileptic patients . Each patient received 90-day supplies of Epitol or Tegretol and placebo , which replaced the usual dosage of the alternate product . Group A consisted of 20 seizure-free ( from 5 months to 2 years ) patients and group B of 20 patients with seizures refractory to drug therapy . In group A , four patients had seizures , two on both Epitol and Tegretol and two on Tegretol . In group B , the average seizure frequencies were 0.25 seizures per day on Epitol and 0.22 seizures per day on Tegretol .  Average seizure frequencies were statistically the same ( at a 20 % difference , p < 0.05 ) . Areas under the curve were statistically the same ( at a 20 % difference , p = 0.05 ) . Average peak heights were statistically the same ( at a 20 % difference , p < 0.05 ) . Average time to peak was earlier with Epitol . Epitol and Tegretol performed equally well in clinical efficacy and bioequivalency Abstract Purpose . To determine if three marketed generic carbamazepine tablets were bioequivalent to the innovator formulation , as well as to each other . In addition , to examine in vivo-in vitro relationships among the four formulations . Methods . Each formulation was given as a single dose to 18 healthy male and female subjects using a crossover design . Blood sample s were collected for 169 hr . Carbamazepine was assayed by HPLC with UV detection . Results .In vivo fraction absorbed plots indicated that the three generic formulations were absorbed more rapidly than the innovator product , and the mean time of maximum plasma concentration was 6−7 hr sooner for the generic formulations . The mean maximum plasma concentration ranged from 17−19 percent higher for the generic products compared to the innovator , and the 90 % confidence limits for Cmax data ranged from 111 % to 126 % . The mean AUC(0−∞ ) for the generic products ranged from 101−104 % compared to the innovator , and the confidence limits for AUC ranged from 97−108 % . Conclusions . The generic products were all more rapidly absorbed than the innovator , but simulations of steady-state concentrations indicated that it would be unlikely that these differences would have any significant clinical effect . An excellent association was seen between the Cmax and the percent of drug dissolved in vitro . The correlation was used to accurately predict the Cmax of four other 200 mg tablets evaluated in an earlier study Carbamazepine is among those drugs that have been considered to have a narrow therapeutic plasma concentration range , that is , a narrow therapeutic index . Although the US Food and Drug Administration has approved new generic products based on st and ard single‐dose bioequivalence studies , several state formularies , including the New Jersey Drug Utilization Review Council , have recently established additional criteria for acceptance of bioequivalence of narrow therapeutic index drugs , limiting the use of some approved generic drugs in specific states . To further vali date the adequacy of single‐dose studies for the determination of bioequivalence of narrow therapeutic index drugs , a multiple‐dose study was conducted that more closely reflected therapeutic use The relative bioavailability of four different carbamazepine products , showing large differences in in vitro dissolution profiles , was studied in healthy volunteers to correlate the occurrence of side effects with a measure of the rate of absorption in vivo for bioequivalence testing . Two of the three generic products investigated showed bioequivalence with respect to the extent of absorption with Tegretol ® . In vivo , the differences found in absorption rate were reflected in the occurrence of side effects , especially dizziness . As a measure for the rate of absorption , the partial AUC did not seem to be a good characteristic to test bioequivalence , as the variability is very high and dependent on the AUC taken . The Cmax/AUCpart seems more promising , especially the partial AUC directly after completion of the absorption process . The variability is low in the case of carbamazepine after a single dose . However , as long as no consensus on the use of other metrics and the objective ( clinical or quality control aspects ) of bioequivalence testing is reached , and no other pharmacokinetic characteristic is vali date d , Cmax should be the characteristic of choice for the rate of absorption in single‐dose studies with carbamazepine products . Copyright © 1999 John Wiley & Sons , 
    Output:
    
Prospect i ve studies in patients showed no differences between br and and generic drugs in PK parameters of bioequivalence .
Comparison of br and and generic drugs revealed no significant difference in seizure frequency ; however , some prospect i ve studies showed significant differences in PK parameters , primarily those not used for bioequivalence determinations .
The highest levels of evidence indicate that there should not be a problem with generic substitution , although some patients are more prone to problems with the generic products .
Some evidence suggests that switches between multiple generic AED products in certain individuals may be problematic