Bioavailability of Orally Administered Drugs in Critically Ill Patients

Forsberg, Johanna; Bedard, Emma; Mahmoud, Sherif Hanafy

doi:10.1177/08971900221100205

Cited by 13 publications

(4 citation statements)

References 77 publications

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“…The primary weaknesses of OAT are inter-individual variability in the clinical outcomes and AMR owing to inter-individual variability in pharmacokinetics [25,29,30,[96][97][98] and hepatobiliary vs. renal clearance [20] delaying the achievement of the minimum inhibitory concentration (MIC) in urine [23,87]. The oral bioavailability of OAT differs with race [32,99], food intake [97], inter-individual variability in the gastric emptying time [100], posture (supine or ambulatory) [101,102], and the general health status of the patient [103]. MIC is the lowest antimicrobial concentration required to prevent the visible growth of the test strain of a microbe after a definite incubation period under strictly controlled in vitro conditions [104].…”

Section: Swots Of Oral Antimicrobial Therapy (Oat) For Cystitismentioning

confidence: 99%

“…The variability in the initial drug concentration due to variable absorption from the gut [25,32,[96][97][98][99][100][101][102][103], hepatobiliary vs. renal clearance delaying the achievement of the MIC in urine [20,23,28,30,87,101,105,109], and variability in urine in-flow rate of 0.3-15 mL/min (~50× difference) [26,56] could reduce the delay in achieving the urinary MIC; B.…”

Section: Root Cause Analysis Of Amr-delay and Variability In Urinary Micmentioning

confidence: 99%

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SWOT and Root Cause Analyses of Antimicrobial Resistance to Oral Antimicrobial Treatment of Cystitis

Tyagi,

Stewart

et al. 2024

Antibiotics

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Nearly 150 million cases of urinary tract infections (UTIs) are reported each year, of which uncomplicated cystitis triggers > 25% of outpatient prescriptions of oral antimicrobial treatment (OAT). OAT aids immune cells infiltrating the urothelium in eliminating uropathogens capable of invading the urothelium and surviving hyperosmotic urine. This self-evident adaptability of uropathogens and the short interval between the introduction of Penicillin and the first report of antimicrobial resistance (AMR) implicate AMR as an evolutionary conserved heritable trait of mutant strains selected by the Darwinian principle to survive environmental threats through exponential proliferation. Therefore, AMR can only be countered by antimicrobial stewardship (AMS) following the principle of the five Ds—drug, dose, duration, drug route, and de-escalation. While convenient to administer, the onset of the minimum inhibitory concentration (MIC) for OAT in urine leaves a window of opportunity for uropathogens to survive the first contact with an antimicrobial and arm their descendant colonies with AMR for surviving subsequent higher urine antimicrobial levels. Meanwhile, the initial dose of intravesical antimicrobial treatment (IAT) may be well above the MIC. Therefore, the widespread clinical use of OAT for cystitis warrants an analysis of the strengths, weaknesses, opportunity, and threats (SWOTs) and a root cause analysis of the AMR associated with OAT and IAT.

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Section: Swots Of Oral Antimicrobial Therapy (Oat) For Cystitismentioning

confidence: 99%

Section: Root Cause Analysis Of Amr-delay and Variability In Urinary Micmentioning

confidence: 99%

SWOT and Root Cause Analyses of Antimicrobial Resistance to Oral Antimicrobial Treatment of Cystitis

Tyagi,

Stewart

et al. 2024

Antibiotics

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“…We investigated the absorption and metabolism of enterally administered esomeprazole compared to intravenously administered esomeprazole in patients treated for cardiogenic shock compared to elective cardiac surgical patients before and after surgery, as there is a lack of valid knowledge on this issue [20].…”

Section: Introductionmentioning

confidence: 99%

Oral Drug Absorption and Drug Disposition in Critically Ill Cardiac Patients

Harnisch,

Brockmöller,

Hapke

et al. 2023

Pharmaceutics

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(1) Background: In critically ill cardiac patients, parenteral and enteral food and drug administration routes may be used. However, it is not well known how drug absorption and metabolism are altered in this group of adult patients. Here, we analyze drug absorption and metabolism in patients after cardiogenic shock using the pharmacokinetics of therapeutically indicated esomeprazole. (2) Methods: The pharmacokinetics of esomeprazole were analyzed in a consecutive series of patients with cardiogenic shock and controls before and after elective cardiac surgery. Esomeprazole was administered orally or with a nasogastric tube and once as an intravenous infusion. (3) Results: The maximum plasma concentration and AUC of esomeprazole were, on average, only half in critically ill patients compared with controls (p < 0.005) and remained lower even seven days later. Interestingly, esomeprazole absorption was also markedly compromised on day 1 after elective surgery. The metabolites of esomeprazole showed a high variability between patients. The esomeprazole sulfone/esomeprazole ratio reflecting CYP3A4 activity was significantly lower in critically ill patients even up to day 7, and this ratio was negatively correlated with CRP values (p = 0.002). The 5′-OH-esomeprazole and 5-O-desmethyl-esomeprazol ratios reflecting CYP2C19 activity did not differ significantly between critically ill and control patients. (4) Conclusions: Gastrointestinal drug absorption can be significantly reduced in critically ill cardiac patients compared with elective patients with stable cardiovascular disease. The decrease in bioavailability indicates that, under these conditions, any vital medication should be administered intravenously to maintain high levels of medications. After shock, hepatic metabolism via the CYP3A4 enzyme may be reduced.

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“…However, absorption via the gastrointestinal is highly variable in the critically ill. This is because of altered gastrointestinal perfusion, changes in gastric pH, drug interactions, and altered gastrointestinal motility (4). The latter effect may be mediated by opioids, which may decrease gastrointestinal absorption (5).…”

mentioning

confidence: 99%

Effectiveness of Sublingual Buprenorphine for Pain Control in the ICU*

Patanwala,

Moran,

Johnstone

et al. 2023

Critical Care Medicine

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OBJECTIVES: The objective of this study was to compare pain control and opioid consumption in critically ill patients who were treated with buprenorphine sublingual or oxycodone oral/enteral during ICU admission. DESIGN: This was a retrospective, parallel, cohort study. SETTING: General medical or surgical ICUs of a quaternary, urban hospital in Sydney, NSW, Australia. PATIENTS: Data were obtained for all patients admitted to two general medical or surgical ICU from January 2019 to January 2023. Patients were grouped as those who received buprenorphine sublingual versus oxycodone oral/enteral. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pain control was compared between a propensity score matched cohort of patients who received buprenorphine versus oxycodone. The primary outcome was the probability of significant pain. A significant pain score was defined as greater than or equal to 4 on the 0–10 Numeric Rating Scale or greater than or equal to 6 on the Behavioral Pain Scale. The study cohort included 1,070 patients (288 buprenorphine and 782 oxycodone). After propensity score matching, there were 288 patients in each group. The mean age of the matched cohort was 64 ± 16 years, 295 (51%) were male, and 359 (62%) had a surgical admission. The median probability of significant pain was 0.16 with buprenorphine and 0.17 with oxycodone (median difference, 0.01; 95% CI, –0.02 to 0.04; p = 0.50). Median opioid consumption in oral morphine milligram equivalents (MMEs) was 65 with buprenorphine and 70 with oxycodone (median difference, –1 mg; 95% CI, –10 to 10 mg; p = 0.73). Median MME per ICU day was 22 with buprenorphine and 22 with oxycodone (median difference, 1 mg; 95% CI, –2 to 5 mg; p = 0.38). CONCLUSIONS: Buprenorphine sublingual is as effective as oxycodone oral/enteral with regard to pain control and opioid consumption in the ICU. Buprenorphine sublingual is an appropriate option for patients in the ICU who are unable to take oral/enteral medications.

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Bioavailability of Orally Administered Drugs in Critically Ill Patients

Cited by 13 publications

References 77 publications

SWOT and Root Cause Analyses of Antimicrobial Resistance to Oral Antimicrobial Treatment of Cystitis

SWOT and Root Cause Analyses of Antimicrobial Resistance to Oral Antimicrobial Treatment of Cystitis

Oral Drug Absorption and Drug Disposition in Critically Ill Cardiac Patients

Effectiveness of Sublingual Buprenorphine for Pain Control in the ICU*

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