Effects of hepatic function on vancomycin clinical pharmacology

Brown, Nita S.; Ho, Dah Hsi; Fong, K. L.L.; Bogerd, L.; Maksymiuk, Andrew W.; Bolivar, Ricardo; Fainstein, Victor; Bodey, Gerald P.

doi:10.1128/aac.23.4.603

Cited by 68 publications

(43 citation statements)

References 19 publications

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“…The PK profiles of vancomycin were also simulated using the liver cirrhosis population model (Child‐Pugh scores for mild level of cirrhosis, score level A; CP‐A), which is implemented in the Simcyp software. The clinical observations in patients with abnormal liver functions were predominantly within the 5th to 95th percentiles of these simulations ( Figure 3 e 24). …”

Section: Resultsmentioning

confidence: 60%

“…On the other hand, a decrease in albumin concentration results in an increase in clearance through an increase in free fraction of the drug. In this study, simulation with the CP‐A system model was well‐predicted for the PK profile of vancomycin in patients with abnormal liver function who showed an increase in vancomycin trough concentration 24. Therefore, multiple physiological changes that are due to liver dysfunction showed a potential to influence the distribution and elimination of vancomycin.…”

Section: Discussionmentioning

confidence: 85%

“…Open circles represent the observed data from reported clinical studies: ( a–d ) Takenaka et al 35. (1993); ( e ) Brown et al 24. (1983).…”

Section: Resultsmentioning

confidence: 99%

“…Hepatic elimination seems to have a limited contribution to the PK of vancomycin due to a lack of metabolic data. Nevertheless, Brown et al 24. (1983) reported that vancomycin PK in patients with abnormal liver functions was significantly different from that in patients with normal liver function.…”

Section: Discussionmentioning

confidence: 99%

“…The lung:plasma partition coefficient predicted by the Simcyp simulator was also evaluated by comparing the observed AUC ELF,0–∞ /AUC plasma,0–∞ ratio of vancomycin. In addition, the model evaluation using the observations reported by Brown et al 24. was conducted based on the simulation with Sim‐Cirrhosis CP‐A population file.…”

Section: Methodsmentioning

confidence: 99%

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Using a Vancomycin PBPK Model in Special Populations to Elucidate Case‐Based Clinical PK Observations

Emoto

Johnson

McPhail

et al. 2018

CPT Pharmacom & Syst Pharma

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Simultaneous changes in several physiological factors may contribute to the large pharmacokinetic (PK) variability of vancomycin. This study was designed to systematically characterize the effects of multiple physiological factors to the altered PK of vancomycin observed in special populations. A vancomycin physiologically based pharmacokinetic (PBPK) model was developed as a PK simulation platform to quantitatively assess the effects of changes in physiologies to the PK profiles. The developed model predicted the concentration‐time profiles in healthy adults and diseased patients. The implementation of developmental changes in both renal and non‐renal elimination pathways to the pediatric model improved the predictability of vancomycin clearance. Simulated PK profiles with a 50% decrease in cardiac output (peak plasma concentration (Cmax), 59.9 ng/mL) were similar to those observed in patients before bypass surgery (Cmax, 55.1 ng/mL). The PBPK modeling of vancomycin demonstrated its potential to provide mechanistic insights into the altered disposition observed in patients who have changes in multiple physiological factors.

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Section: Resultsmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 85%

“…Open circles represent the observed data from reported clinical studies: ( a–d ) Takenaka et al 35. (1993); ( e ) Brown et al 24. (1983).…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Using a Vancomycin PBPK Model in Special Populations to Elucidate Case‐Based Clinical PK Observations

Emoto

Johnson

McPhail

et al. 2018

CPT Pharmacom & Syst Pharma

View full text Add to dashboard Cite

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Vancomycin Pharmacokinetics in Small, Seriously Ill Infants

Naqvi¹

1986

Arch Pediatr Adolesc Med

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Vancomycin: An Update

Cheung

DiPiro

1986

Pharmacotherapy

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Vancomycin is a narrow-spectrum glycopeptide antibiotic with potent antistaphylococcal activity. It is primarily active against gram-positive organisms. Bacterial resistance rarely develops due to its numerous modes of action. The toxic potential of vancomycin is less significant than previously thought. "Red neck syndrome" seems to be the most common side effect and appears to be caused by rapid intravenous infusion. It is characterized by erythema at the base of the neck and the upper back; hypotensive episodes may also occur. Nephrotoxicity and ototoxicity are rare. Relationships between toxicities and serum concentrations have not been established. The disposition of vancomycin after intravenous administration proceeds biphasically--rapid distribution followed by elimination. The drug is excreted primarily unchanged in the urine by glomerular filtration. Vancomycin clearance is reduced and elimination half-life is prolonged in patients with renal insufficiency. Various methods have been published to aid in dosing the drug in these patients. Vancomycin is the drug of choice in the treatment of methicillin-resistant staphylococcal infections. It is also useful in the treatment of gram-positive endocarditis and has been used as alternative therapy in the treatment of prophylaxis of gram-positive infections in penicillin-allergic patients. Oral vancomycin is the preferred therapy in antibiotic-associated colitis.

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Effects of hepatic function on vancomycin clinical pharmacology

Cited by 68 publications

References 19 publications

Using a Vancomycin PBPK Model in Special Populations to Elucidate Case‐Based Clinical PK Observations

Using a Vancomycin PBPK Model in Special Populations to Elucidate Case‐Based Clinical PK Observations

Vancomycin Pharmacokinetics in Small, Seriously Ill Infants

Vancomycin: An Update

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