Propofol increases the rate of albumin-unbound free midazolam in serum albumin solution

Ohmori, Jun; Miyagawa, Shigeru; Higuchi, Hitoshi; Ishii, Minako; Arai, Yukiko; Kohjitani, Atsushi; Shimada, Masahiko; Miyawaki, Takuya

doi:10.1007/s00540-011-1176-6

Cited by 18 publications

(6 citation statements)

References 13 publications

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“…The absence of propofol peaks at such high concentrations brings up an interesting aspect of propofol biochemistry; namely, that propofol is known to complex with proteins in serum. 4,30,31 The protein–propofol complexation competes with PDMS for the accumulation of propofol, reducing the SPME effect. The quantitative traits of this competitive partitioning warrants further study.…”

Section: Resultsmentioning

confidence: 99%

Separation and Enhanced Detection of Anesthetic Compounds Using Solid Phase Micro-Extraction (SPME)–Raman Spectroscopy

Nwaneshiudu

Schwartz

2014

Appl Spectrosc

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Polydimethylsiloxane (PDMS)-based solid-phase micro-extraction (SPME) was used along with Raman spectroscopy (RS) to separate and enhance the detection of five anesthetic compounds (halothane, propofol, isoflurane, enflurane, and etomidate) from aqueous and serum phases. Raman signals in the spectral ranges 250-450 cm(-1) and 950-1050 cm(-1) allowed the unique characterization of all five compounds when extracted into the PDMS phase. The SPME-RS detection of clinically relevant concentrations of aqueous propofol (6.5 μM) and halothane (200 μM) is shown. We quantify the partition coefficient for aqueous halothane in PDMS as log K = 1.9 ± 0.2. Solid-phase micro-extraction of the anesthetics makes their detection possible without the strong autofluorescent interference of serum proteins. Because of low solubility and/or weak Raman scattering, we found it challenging to detect enflurane, isoflurane, and etomidate directly from the aqueous phase, but could we do so with SPME enhancement. These studies show the potential of SPME-RS as a method for the direct detection of anesthetics in blood.

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Section: Resultsmentioning

confidence: 99%

Separation and Enhanced Detection of Anesthetic Compounds Using Solid Phase Micro-Extraction (SPME)–Raman Spectroscopy

Nwaneshiudu

Schwartz

2014

Appl Spectrosc

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“…The protein binding rates of remimazolam and propofol are 92% [ 18 ] and 98% [ 19 , 20 ], respectively. Propofol causes an increase in midazolam blood concentrations [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Randomized controlled trial for anesthesia during gastroscopy: interactions between remimazolam and propofol in combination with sufentanil

et al. 2023

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Background Remimazolam is a new short-duration anesthetic currently used for gastroscopy and can be mixed with propofol and potent opioids. Aim The study aimed to investigate the synergistic interaction between remimazolam and propofol after sufentanil administration and to determine the appropriate dose ratios between remimazolam and propofol. Method This study used a randomized controlled design. Patients scheduled for gastrointestinal endoscopy were included and randomized into five groups. The randomized block design was applied at a randomization ratio of 1:1. Patients in each group received sufentanil (0.1 μg/kg) and the calculated doses of remimazolam and propofol. Using the up and down method, the median effective dose (ED50) and the 95% confidence interval (CI) were determined based on whether the eyelash reflex disappeared in each treatment group. Isobolographic analysis was used to analyze the presence of drug interactions. The interaction coefficient and the dose ratio between remimazolam and propofol were calculated by algebraic analysis. Statistical analysis was performed using interval estimates and 95% CI for statistical attributes. Results Cross-sectional analysis of the isobologram showed a clinically significant synergistic effect between remimazolam and propofol. When 0.016, 0.032, and 0.047 mg/kg of remimazolam were combined with 0.477, 0.221, and 0.131 mg/kg of propofol, the interaction coefficients were 1.04, 1.21, and 1.06, respectively. The dose ratio of remimazolam to propofol was approximately 1:7. Conclusion Remimazolam and propofol have synergistic clinical effects. A strong synergistic effect was observed when the remimazolam and propofol dose ratio was 1:7 (mg/kg). Clinical trial The study protocol was registered at the Chinese Clinical Trial Registry (ChiCTR2100052425).

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“…This mechanistic interpretation is consistent with the results of the present study. Moreover, one study reported that propofol competitively reduced the rate of albumin binding with midazolam (Ohmori et al, 2011 ). Competitive drug interactions between these two drugs may also underlie the results of the present study because propofol and BZD bind strongly to serum proteins.…”

Section: Discussionmentioning

confidence: 99%

Cross‐sectional study of propofol dose during intravenous sedation for dental surgery in patients with long‐term oral benzodiazepine therapy: A secondary publication

Fujisawa

Miyata

Nitta

et al. 2022

Clinical & Exp Dental Res

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Objectives The amount of propofol required for intravenous sedation (IVS) in patients on long‐term oral benzodiazepine (BZD) therapy may be affected by drug interactions and central changes in sensitivity. However, there is no research on the effect of long‐term oral BZD use on the amount of propofol required for IVS. We aimed to clarify the difference between the total propofol dose required for IVS in patients with or without long‐term oral BZD therapy. Material and methods Among patients treated for 4 years, the total administered dose required for IVS with propofol alone and local anesthesia for the extraction of bilateral impacted mandibular wisdom teeth, was retrospectively compared between patients with continuous oral BZD use for ≥6 months (BZD group; n = 24) and those without such use (control group; n = 307). The aimed sedation level was the Ramsay sedation scale 3–4. Results The amount of propofol required for IVS was significantly lower in the BZD group compared to the control group (4.83 ± 1.30 vs. 5.91 ± 1.25 mg/kg/h, p < .001; 95% confidence interval, −1.22 to −0.94 mg/kg/h; Cohen's d, 0.84). The required propofol dose was not influenced by preoperative oral BZD administration on the day of extraction (presence [n = 13] vs. absence [n = 11]: 4.9 ± 1.3 vs. 4.8 ± 1.7 mg/kg/h, p = .83). Long‐term oral BZD therapy remained a significant factor for a lower required propofol dose after adjusting for age with multiple linear regression analysis. The underlying mechanism cannot be an additive action process but might pertain to competitive inhibition via an enzyme involved in glucuronate conjugation or competitive albumin binding. Conclusions Clinicians should understand that patients on long‐term oral BZDs therapy might require less propofol for IVS than those not on BZDs, irrespective of whether BZDs were taken preoperatively on the day of surgery.

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Propofol increases the rate of albumin-unbound free midazolam in serum albumin solution

Cited by 18 publications

References 13 publications

Separation and Enhanced Detection of Anesthetic Compounds Using Solid Phase Micro-Extraction (SPME)–Raman Spectroscopy

Separation and Enhanced Detection of Anesthetic Compounds Using Solid Phase Micro-Extraction (SPME)–Raman Spectroscopy

Randomized controlled trial for anesthesia during gastroscopy: interactions between remimazolam and propofol in combination with sufentanil

Cross‐sectional study of propofol dose during intravenous sedation for dental surgery in patients with long‐term oral benzodiazepine therapy: A secondary publication

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