Long-term effects of gastric bypass and duodenal switch on systemic exposure of atorvastatin

Abstract

BackgroundA 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 aimed to investigate the long-term effects on systemic exposure of atorvastatin acid in the same group of patients.MethodsAn 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.ResultsThe 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.ConclusionsThe 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. ClinicalTrial NCT00331565.

The influence of bariatric surgery on oral drug bioavailability in patients with obesity: A systematic review

“…RYGBP was the predominant surgical procedure (n = 18) . In one study, BPD was investigated as the surgical procedure, while two studies investigated BPD‐DS, six studied SG, and one included jejunoileostomy …”

“…Among the 22 studies, 16 utilized a single‐dose design, administering a given dose of the studied drug on the day of the pharmacokinetic study intervention. In the remaining six studies, patients were investigated in steady state . Several drugs were studied because of their status as probe drugs/substrates for different CYP enzymes and drug transporters, eg, midazolam for CYP3A as well as digoxin for P‐gp .…”

“…However, since the disposition of atorvastatin is also affected both by uptake (organic anion transporting peptides, OATPs) and efflux (P‐gp) transporters in the liver, atorvastatin is a less selective probe drug than midazolam to study CYP3A activity. The impact of bariatric surgery on the pharmacokinetics of atorvastatin both in the short term (3‐8 wk) and long term (2 y) was investigated in three studies . RYGBP produced a variable effect on the individual systemic exposure of atorvastatin, ranging from a threefold decrease to a twofold increase 3 to 6 weeks following surgery .…”

Practical Recommendations of the Obesity Management Task Force of the European Association for the Study of Obesity for the Post-Bariatric Surgery Medical Management

“…One of the few studies addressing this issue demonstrated that the systemic exposure of atorvastatin showed a significant change over time after bariatric surgery, albeit with large inter- and intra-individual 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 during the first years after gastric bypass and duodenal switch [77]. …”

“…However, treatment with statins should be initiated if treatment targets are not met on lifestyle intervention [64]. Since the long-term effect of bariatric surgery on the absorption and pharmacokinetics of statins is largely unknown [76], patients on statins should be treated with the lowest dose possible while monitoring the plasma lipid profile [76,77]. One of the few studies addressing this issue demonstrated that the systemic exposure of atorvastatin showed a significant change over time after bariatric surgery, albeit with large inter- and intra-individual variations.…”