human
***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: AIMS Roux-en-Y gastric bypass ( RYGB ) alters the anatomical structure of the gastrointestinal tract , which can result in alterations in drug disposition . The aim of the present study was to evaluate the oral disposition of two compounds belonging to the Biopharmaceutical Classification System Class II - fenofibrate ( bile salt-dependent solubility ) and posaconazole ( gastric pH-dependent dissolution ) - before and after RYGB in the same individuals . METHODS A single-dose pharmacokinetic study with two model compounds - namely , 67 mg fenofibrate ( Lipanthyl ® ) and 400 mg posaconazole ( Noxafil ® ) - was performed in 12 volunteers pre- and post-RYGB . After oral administration , blood sample s were collected at different time points up to 48 h after administration . Plasma concentrations were determined by high-performance liquid chromatography in order to calculate the area under the concentration-time curve up to 48 h ( AUC0 - 48 h ) , the peak plasma concentration ( Cmax ) and the time to reach peak concentration ( Tmax ) . RESULTS After administration of fenofibrate , no relevant differences in AUC0 - 48 h , Cmax and Tmax between the pre- and postoperative setting were observed . The geometric mean of the ratio of AUC0 - 48 h post/pre-RYGB for fenofibrate was 1.10 [ 95 % confidence interval ( CI ) 0.87 , 1.40 ; P = 0.40 ] . For posaconazole , an important decrease in AUC0 - 48 h and Cmax following RYGB was shown ; the geometric mean of the AUC0 - 48 h post/pre-RYGB ratio was 0.68 ( 95 % CI 0.48 , 0.96 ; P = 0.03 ) and the geometric mean of the Cmax pre/post-RYGB ratio was 0.60 ( 95 % CI 0.39 , 0.94 ; P = 0.03 ) . The decreased exposure of posaconazole could be explained by the increased gastric pH and accelerated gastric emptying of fluids post-RYGB . No difference for Tmax was observed . CONCLUSIONS The disposition of fenofibrate was not altered after RYGB , whereas the oral disposition of posaconazole was significantly decreased following RYGB AIMS Venous thromboembolism is an important cause of postoperative morbidity and mortality in bariatric surgery . Studies of direct oral anticoagulants ( DOACs ) are not available in this surgical field . The objective of this phase 1 clinical trial was to investigate pharmacokinetic and pharmacodynamic ( PK/PD ) parameters of rivaroxaban in bariatric patients . METHODS In this single-centre study , obese patients received single oral doses of rivaroxaban ( 10 mg ) 1 day prior to and 3 days after bariatric surgery . PK and PD parameters were assessed at baseline and during 24 h after drug ingestion . RESULTS Six Roux-en-Y gastric bypass patients and six sleeve gastrectomy patients completed the study .  Mean rivaroxaban area under plasma concentration-time curve , peak plasma concentration , time to peak plasma concentration and terminal half-life were 971.9 μg·h l-1 ( coefficient of variation : 10.6 ) , 135.3 μg l-1 ( 26.7 ) , 1.5 h and 13.1 h ( 34.1 ) prior to and 1165.8 ( 21.9 ) , 170.0 ( 15.9 ) , 1.5 and 8.9 ( 44.6 ) postsurgery for SG patients and 933.7 μg·h l-1 ( 22.3 ) , 136.5 μg l-1 ( 10.7 ) , 1.5 h und 13.8 h ( 46.6 ) prior to and 1029.4 ( 7.4 ) , 110.8 ( 31.8 ) , 2.5 and 15 ( 60.0 ) postsurgery for Roux-en-Y gastric bypass patients , respectively . Prothrombin fragments ( F1 + 2 ) decreased during the first 12 hours and increased thereafter in the pre- and the postbariatric setting . Thrombin-antithrombin complexes dropped within 1 - 3 h in the prebariatric setting and remained low after surgery until they increased at 24 h postdose  . Rivaroxaban was well tolerated and no relevant safety issues were observed . CONCLUSIONS Bariatric surgery does not appear to alter PK of rivaroxaban in a clinical ly relevant way . Effective prophylactic postbariatric anticoagulation is supported by changes in PD Background A previous study of 22 patients undergoing either gastric bypass or duodenal switch showed increased systemic exposure of atorvastatin acid  3–8 weeks after surgery in the majority of patients . This study aim ed to investigate the long-term effects on systemic exposure of atorvastatin acid in the same group of patients . Methods An 8-h pharmacokinetic investigation was performed a median of 27 months ( range 21–45 months ) after surgery . Systemic exposure was measured as the area under the plasma concentration versus the time curve from 0 to 8 h postdose ( AUC0–8 ) . Linear mixed models with AUC0–8 as the dependent variable were implemented to assess the effect of time , surgical procedure , and body mass index ( BMI ) as explanatory variables . Results The study enrolled 20 patients . The systemic exposure of atorvastatin acid changed significantly over time ( p = 0.001 ) , albeit there was substantial variation between subjects . The effect of time was attenuated but remained significant after adjustment for surgical procedure and BMI ( p = 0.048 ) . The initial AUC0–8 increase seen in the majority of patients 3–8 weeks after surgery was normalized long term , with 7 of the 12 gastric bypass patients and 6 of the 8 duodenal switch patients showing decreased AUC0–8 compared with preoperative values . Conclusions The systemic exposure of atorvastatin showed a significant change over time after bariatric surgery , albeit with large inter- and intraindividual variations . The findings indicate that patients using  atorvastatin  or drugs with similar pharmacokinetic properties should be monitored closely for both therapeutic effects and adverse events the first years after gastric bypass and duodenal switch . Clinical Trial NCT00331565 Background Data on the absorption of orally administered drugs following  Roux-en-Y gastric bypass ( RYGB ) surgery in obese patients are limited and inconclusive . As it is difficult to predict changes in absorption , studies on frequently used drugs in this population are necessary . Acetylsalicylic acid ( ASA ) and omeprazole are two commonly prescribed drugs in obese patients . Methods In this repeated measures study , omeprazole and salicylic acid ( SA ) serum concentrations were measured before and after RYGB in 34 morbidly obese subjects .  Time to maximum concentration ( Tmax ) , lag time ( Tlag ) , maximum concentration ( Cmax ) , and area under the serum concentration versus time curve ( AUC ) were calculated for both drugs to determine possible differences in drug absorption after the procedure . Results For SA , Tmax significantly decreased after RYGB , while both Cmax and AUC0–24 significantly increased . For omeprazole , both Tmax and Tlag significantly decreased after RYGB , while Cmax significantly increased . Mean AUC0–12 significantly decreased post-surgery . The difference in AUC0–12 before and after surgery varied between subjects . Conclusions Our study shows a faster absorption of both ASA and omeprazole after RYGB . The exposure to ASA is higher post-surgery , but the st and ard dose of 80 mg does not need to be modified , considering its range in effective dose . The exposure to omeprazole is , on average , decreased after surgery . Clinicians should be aware to increase the dose of omeprazole if symptoms suggest inadequate response Biliopancreatic diversion with duodenal switch is a combined restrictive and malabsorptive surgical weight loss procedure . Given that this procedure introduces a bypass of the proximal small intestine , it is a suitable model for investigating the influence of the proximal intestine on drug bioavailability . Eight‐hour pharmacokinetic profiles were obtained the day before surgery and again after surgery at ( median ) 6 weeks ( range , 4–8 weeks ) in 10 morbidly obese patients who were receiving treatment with 20–80 mg atorvastatin each morning .  The bioavailability of atorvastatin  acid was significantly increased , with a mean twofold higher AUC0–8 after surgery ( range 1.0–4.2 , P = 0.001 ) . Time to maximum plasma concentration ( Cmax ) increased from 1.2 h before surgery to 2.3 h after surgery ( P = 0.03 ) . The results emphasize the protective nature of the proximal small intestine against ingested exogenous compounds . Consequently , retitration to the lowest effective dose should be considered after biliopancreatic diversion with duodenal switch in the case of drugs with a high degree of intestinal first pass metabolism and a narrow therapeutic window AIMS Our objective was to study in vivo the role of CYP2C and CYP3A4 in the disposition of 3-keto-desogestrel after administration of desogestrel , by using the selective inhibitors fluconazole ( CYP2C ) and itraconazole ( CYP3A4 ) . METHODS This study had a three-way crossover design and included 12 healthy females , the data from 11 of whom were analyzed . In the first ( control ) phase all subjects received a single 150 microg oral dose of desogestrel alone . In the second and third phases subjects received a 4 day pretreatment with either 200 mg fluconazole or 200 mg itraconazole once daily in a r and omized balanced order . Desogestrel was given 1 h after the last dose of the CYP inhibitor . Plasma 3-keto-desogestrel concentrations were determined for up to 72 h post dose . RESULTS Pretreatment with itraconazole for 4 days significantly increased the area under the plasma concentration-time curve ( AUC ) of 3-keto-desogestrel by 72.4 % ( 95 % confidence interval on the difference 12 % , 133 % ; P = 0.024 ) compared with the control phase , whereas fluconazole pretreatment had no significant effect ( 95 % CI on the difference -42 % , 34 % ) . Neither enzyme inhibitor affected significantly the maximum concentration ( 95 % CI on the difference 14 % , 124 % for itraconazole and -23 % , 40 % for fluconazole ) or elimination half-life ( 95 % CI on the difference -42 % , 120 % for itraconazole and -24 % , 61 % for fluconazole ) of 3-keto-desogestrel . CONCLUSIONS According to the present study , the biotransformation of desogestrel to 3-keto-desogestrel did not appear to be mediated by CYP2C9 and CYP2C19 as suggested earlier . However , the further metabolism of 3-keto-desogestrel seems to be catalyzed by CYP3A4 Posture has an effect on gastric emptying . In this study , we investigated whether posture influences the delay in gastric emptying induced by opioid analgesics . Ten healthy male subjects underwent 4 gastric emptying studies with the acetaminophen method . On two occasions the subjects were given a continuous infusion of remifentanil ( 0.2 μg · kg−1 · min−1 ) while lying either on the right lateral side in a 20 ° head-up position or on the left lateral side in a 20 ° head-down position . On two other occasions no infusion was given , and the subjects were studied lying in the two positions . When remifentanil was given , there were no significant differences between the two postures in maximal acetaminophen concentration ( right side , 34 μmol · L−1 ; versus left side , 16 μmol · L−1 ) , time taken to reach the maximal concentration ( 94 versus 109 min ) , or area under the serum acetaminophen concentration time curve from 0 to 60 min ( 962 versus 197 min · μmol · L−1 ) . In the control situation , there were differences between the postures in maximal acetaminophen concentration ( 138 versus 94 μmol · L−1 ; P < 0.0001 ) and area under the serum acetaminophen concentration time curves from 0 to 60 min ( 5092 versus 3793 min · μmol · L−1 ; P < 0.0001 ) , but there was no significant difference in time taken to reach the maximal concentration ( 25 versus 47 min ) . Compared with the control situation , remifentanil  delayed gastric emptying in both postures . We conclude that remifentanil  delays gastric emptying and that this delay is not influenced by posture Background : Patients undergoing biliopancreatic diversion ( BPD )  may develop gastric ulcers , particularly within the first postoperative year . The prophylactic use of antisecretory compounds at the usual therapeutic doses , mainly conventional H2-receptor antagonists such as ranit 
    Output:
    
agent
In the case of the majority of studied drugs , an increased absorption rate was observed early after RYGBP .
The effect on systemic exposure allows for a low degree of extrapolation , including between drugs subjected to the same major metabolic and transporter pathways .
***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: AIMS Roux-en-Y gastric bypass ( RYGB ) alters the anatomical structure of the gastrointestinal tract , which can result in alterations in drug disposition . The aim of the present study was to evaluate the oral disposition of two compounds belonging to the Biopharmaceutical Classification System Class II - fenofibrate ( bile salt-dependent solubility ) and posaconazole ( gastric pH-dependent dissolution ) - before and after RYGB in the same individuals . METHODS A single-dose pharmacokinetic study with two model compounds - namely , 67 mg fenofibrate ( Lipanthyl ® ) and 400 mg posaconazole ( Noxafil ® ) - was performed in 12 volunteers pre- and post-RYGB . After oral administration , blood sample s were collected at different time points up to 48 h after administration . Plasma concentrations were determined by high-performance liquid chromatography in order to calculate the area under the concentration-time curve up to 48 h ( AUC0 - 48 h ) , the peak plasma concentration ( Cmax ) and the time to reach peak concentration ( Tmax ) . RESULTS After administration of fenofibrate , no relevant differences in AUC0 - 48 h , Cmax and Tmax between the pre- and postoperative setting were observed . The geometric mean of the ratio of AUC0 - 48 h post/pre-RYGB for fenofibrate was 1.10 [ 95 % confidence interval ( CI ) 0.87 , 1.40 ; P = 0.40 ] . For posaconazole , an important decrease in AUC0 - 48 h and Cmax following RYGB was shown ; the geometric mean of the AUC0 - 48 h post/pre-RYGB ratio was 0.68 ( 95 % CI 0.48 , 0.96 ; P = 0.03 ) and the geometric mean of the Cmax pre/post-RYGB ratio was 0.60 ( 95 % CI 0.39 , 0.94 ; P = 0.03 ) . The decreased exposure of posaconazole could be explained by the increased gastric pH and accelerated gastric emptying of fluids post-RYGB . No difference for Tmax was observed . CONCLUSIONS The disposition of fenofibrate was not altered after RYGB , whereas the oral disposition of posaconazole was significantly decreased following RYGB AIMS Venous thromboembolism is an important cause of postoperative morbidity and mortality in bariatric surgery . Studies of direct oral anticoagulants ( DOACs ) are not available in this surgical field . The objective of this phase 1 clinical trial was to investigate pharmacokinetic and pharmacodynamic ( PK/PD ) parameters of rivaroxaban in bariatric patients . METHODS In this single-centre study , obese patients received single oral doses of rivaroxaban ( 10 mg ) 1 day prior to and 3 days after bariatric surgery . PK and PD parameters were assessed at baseline and during 24 h after drug ingestion . RESULTS Six Roux-en-Y gastric bypass patients and six sleeve gastrectomy patients completed the study .  Mean rivaroxaban area under plasma concentration-time curve , peak plasma concentration , time to peak plasma concentration and terminal half-life were 971.9 μg·h l-1 ( coefficient of variation : 10.6 ) , 135.3 μg l-1 ( 26.7 ) , 1.5 h and 13.1 h ( 34.1 ) prior to and 1165.8 ( 21.9 ) , 170.0 ( 15.9 ) , 1.5 and 8.9 ( 44.6 ) postsurgery for SG patients and 933.7 μg·h l-1 ( 22.3 ) , 136.5 μg l-1 ( 10.7 ) , 1.5 h und 13.8 h ( 46.6 ) prior to and 1029.4 ( 7.4 ) , 110.8 ( 31.8 ) , 2.5 and 15 ( 60.0 ) postsurgery for Roux-en-Y gastric bypass patients , respectively . Prothrombin fragments ( F1 + 2 ) decreased during the first 12 hours and increased thereafter in the pre- and the postbariatric setting . Thrombin-antithrombin complexes dropped within 1 - 3 h in the prebariatric setting and remained low after surgery until they increased at 24 h postdose  . Rivaroxaban was well tolerated and no relevant safety issues were observed . CONCLUSIONS Bariatric surgery does not appear to alter PK of rivaroxaban in a clinical ly relevant way . Effective prophylactic postbariatric anticoagulation is supported by changes in PD Background A previous study of 22 patients undergoing either gastric bypass or duodenal switch showed increased systemic exposure of atorvastatin acid  3–8 weeks after surgery in the majority of patients . This study aim ed to investigate the long-term effects on systemic exposure of atorvastatin acid in the same group of patients . Methods An 8-h pharmacokinetic investigation was performed a median of 27 months ( range 21–45 months ) after surgery . Systemic exposure was measured as the area under the plasma concentration versus the time curve from 0 to 8 h postdose ( AUC0–8 ) . Linear mixed models with AUC0–8 as the dependent variable were implemented to assess the effect of time , surgical procedure , and body mass index ( BMI ) as explanatory variables . Results The study enrolled 20 patients . The systemic exposure of atorvastatin acid changed significantly over time ( p = 0.001 ) , albeit there was substantial variation between subjects . The effect of time was attenuated but remained significant after adjustment for surgical procedure and BMI ( p = 0.048 ) . The initial AUC0–8 increase seen in the majority of patients 3–8 weeks after surgery was normalized long term , with 7 of the 12 gastric bypass patients and 6 of the 8 duodenal switch patients showing decreased AUC0–8 compared with preoperative values . Conclusions The systemic exposure of atorvastatin showed a significant change over time after bariatric surgery , albeit with large inter- and intraindividual variations . The findings indicate that patients using  atorvastatin  or drugs with similar pharmacokinetic properties should be monitored closely for both therapeutic effects and adverse events the first years after gastric bypass and duodenal switch . Clinical Trial NCT00331565 Background Data on the absorption of orally administered drugs following  Roux-en-Y gastric bypass ( RYGB ) surgery in obese patients are limited and inconclusive . As it is difficult to predict changes in absorption , studies on frequently used drugs in this population are necessary . Acetylsalicylic acid ( ASA ) and omeprazole are two commonly prescribed drugs in obese patients . Methods In this repeated measures study , omeprazole and salicylic acid ( SA ) serum concentrations were measured before and after RYGB in 34 morbidly obese subjects .  Time to maximum concentration ( Tmax ) , lag time ( Tlag ) , maximum concentration ( Cmax ) , and area under the serum concentration versus time curve ( AUC ) were calculated for both drugs to determine possible differences in drug absorption after the procedure . Results For SA , Tmax significantly decreased after RYGB , while both Cmax and AUC0–24 significantly increased . For omeprazole , both Tmax and Tlag significantly decreased after RYGB , while Cmax significantly increased . Mean AUC0–12 significantly decreased post-surgery . The difference in AUC0–12 before and after surgery varied between subjects . Conclusions Our study shows a faster absorption of both ASA and omeprazole after RYGB . The exposure to ASA is higher post-surgery , but the st and ard dose of 80 mg does not need to be modified , considering its range in effective dose . The exposure to omeprazole is , on average , decreased after surgery . Clinicians should be aware to increase the dose of omeprazole if symptoms suggest inadequate response Biliopancreatic diversion with duodenal switch is a combined restrictive and malabsorptive surgical weight loss procedure . Given that this procedure introduces a bypass of the proximal small intestine , it is a suitable model for investigating the influence of the proximal intestine on drug bioavailability . Eight‐hour pharmacokinetic profiles were obtained the day before surgery and again after surgery at ( median ) 6 weeks ( range , 4–8 weeks ) in 10 morbidly obese patients who were receiving treatment with 20–80 mg atorvastatin each morning .  The bioavailability of atorvastatin  acid was significantly increased , with a mean twofold higher AUC0–8 after surgery ( range 1.0–4.2 , P = 0.001 ) . Time to maximum plasma concentration ( Cmax ) increased from 1.2 h before surgery to 2.3 h after surgery ( P = 0.03 ) . The results emphasize the protective nature of the proximal small intestine against ingested exogenous compounds . Consequently , retitration to the lowest effective dose should be considered after biliopancreatic diversion with duodenal switch in the case of drugs with a high degree of intestinal first pass metabolism and a narrow therapeutic window AIMS Our objective was to study in vivo the role of CYP2C and CYP3A4 in the disposition of 3-keto-desogestrel after administration of desogestrel , by using the selective inhibitors fluconazole ( CYP2C ) and itraconazole ( CYP3A4 ) . METHODS This study had a three-way crossover design and included 12 healthy females , the data from 11 of whom were analyzed . In the first ( control ) phase all subjects received a single 150 microg oral dose of desogestrel alone . In the second and third phases subjects received a 4 day pretreatment with either 200 mg fluconazole or 200 mg itraconazole once daily in a r and omized balanced order . Desogestrel was given 1 h after the last dose of the CYP inhibitor . Plasma 3-keto-desogestrel concentrations were determined for up to 72 h post dose . RESULTS Pretreatment with itraconazole for 4 days significantly increased the area under the plasma concentration-time curve ( AUC ) of 3-keto-desogestrel by 72.4 % ( 95 % confidence interval on the difference 12 % , 133 % ; P = 0.024 ) compared with the control phase , whereas fluconazole pretreatment had no significant effect ( 95 % CI on the difference -42 % , 34 % ) . Neither enzyme inhibitor affected significantly the maximum concentration ( 95 % CI on the difference 14 % , 124 % for itraconazole and -23 % , 40 % for fluconazole ) or elimination half-life ( 95 % CI on the difference -42 % , 120 % for itraconazole and -24 % , 61 % for fluconazole ) of 3-keto-desogestrel . CONCLUSIONS According to the present study , the biotransformation of desogestrel to 3-keto-desogestrel did not appear to be mediated by CYP2C9 and CYP2C19 as suggested earlier . However , the further metabolism of 3-keto-desogestrel seems to be catalyzed by CYP3A4 Posture has an effect on gastric emptying . In this study , we investigated whether posture influences the delay in gastric emptying induced by opioid analgesics . Ten healthy male subjects underwent 4 gastric emptying studies with the acetaminophen method . On two occasions the subjects were given a continuous infusion of remifentanil ( 0.2 μg · kg−1 · min−1 ) while lying either on the right lateral side in a 20 ° head-up position or on the left lateral side in a 20 ° head-down position . On two other occasions no infusion was given , and the subjects were studied lying in the two positions . When remifentanil was given , there were no significant differences between the two postures in maximal acetaminophen concentration ( right side , 34 μmol · L−1 ; versus left side , 16 μmol · L−1 ) , time taken to reach the maximal concentration ( 94 versus 109 min ) , or area under the serum acetaminophen concentration time curve from 0 to 60 min ( 962 versus 197 min · μmol · L−1 ) . In the control situation , there were differences between the postures in maximal acetaminophen concentration ( 138 versus 94 μmol · L−1 ; P < 0.0001 ) and area under the serum acetaminophen concentration time curves from 0 to 60 min ( 5092 versus 3793 min · μmol · L−1 ; P < 0.0001 ) , but there was no significant difference in time taken to reach the maximal concentration ( 25 versus 47 min ) . Compared with the control situation , remifentanil  delayed gastric emptying in both postures . We conclude that remifentanil  delays gastric emptying and that this delay is not influenced by posture Background : Patients undergoing biliopancreatic diversion ( BPD )  may develop gastric ulcers , particularly within the first postoperative year . The prophylactic use of antisecretory compounds at the usual therapeutic doses , mainly conventional H2-receptor antagonists such as ranit 
    Output:
    