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S Schiere

Publications and source records attributed to S Schiere.

6 recordsLinked to original sources
PubMed1999

Pharmacokinetics and pharmacokinetic-dynamic relationship between rapacuronium (Org 9487) and its 3-desacetyl metabolite (Org 9488).

UNLABELLED: Rapacuronium (Org 9487) is a rapid-onset and short- to intermediate-acting muscle relaxant. Its 3-desacetyl metabolite, Org 9488, also exerts neuromuscular-blocking activity that may become apparent after prolonged maintenance of relaxation with rapacuronium. In this study, the pharmacokinetic behavior (n = 7) of this metabolite and the pharmacokinetic/pharmacodynamic (PK/PD) relationship of rapacuronium (n = 10) and Org 9488 (n = 7) were investigated in humans. Similar protocols were used for three study groups regarding the anesthetic technique, blood and urine sampling, and pharmacokinetic and PK/PD analyses. The time course of action was measured mechanomyographically using the adductor pollicis muscle. The median clearance of rapacuronium was 7.28 mL x kg(-1) x min(-1) x with an excretion fraction in the urine of 6.2%. The clearance (studied in two groups) of Org 9488 was 1.28 and 1.06 mL x kg(-1) x min(-1) with an excretion fraction in the urine of 51.9% and 53.5%, respectively. The median rate constant of transport between plasma and the biophase of rapacuronium (0.449 min(-1)) is markedly larger than that for Org 9488 (0.105 min(-1)). The modeled concentration in the biophase at 50% effect as a measure of potency is higher for rapacuronium (4.70 microg/mL) than for Org 9488 (1.83 microg/mL). The lower clearance of the metabolite will gradually prolong the time course of the neuromuscular blockade during maintenance with rapacuronium. IMPLICATIONS: We investigated the concentration-time-effect relationship of the relaxant rapacuronium and the contribution of its metabolite. Clearance, rate constant of transport between plasma and the biophase, and modeled concentration in the biophase at 50% effect of rapacuronium are consistent with its rapid onset and short to intermediate duration. The lower clearance of the metabolite will gradually prolong the time course of the neuromuscular blockade during maintenance with rapacuronium.

Adult↗
PubMed1997

[Sodium polystyrene sulfonate (Resonium A) as possible cause of rectal blood loss].

A 67-year-old man underwent laparotomy for a ruptured aneurysm of the abdominal aorta. Postoperatively he was treated with haemodialysis because of perioperatively developed acute renal failure. Hyperkalaemia was temporarily treated with sodium polystyrene sulfonate (Resonium A) after which he lost blood per rectum. A hemicolectomy was necessary because of intractable blood loss due to ulceration of the colon. This complication is related to uraemia and the use of sodium polystyrene sulfonate with or without sorbitol.

Aged↗
PubMed1997

Comparison of vecuronium with ORG 9487 and their interaction.

PURPOSE: To compare the pharmacodynamic behaviour of vecuronium with that of ORG 9487, we measured the time-course of action of equipotent doses of ORG 9487 and vecuronium and investigated their mutual interaction when given in succession. METHODS: Sixty ASA I-II patients were anaesthetized with thiopentone, fentanyl, halothane and nitrous oxide and assigned randomly to four groups. Each patient received an initial dose (ID) of either vecuronium (V) or ORG 9487 (O) followed by maintenance doses (MDn) of either V or O (ID/MD: O/O, V/O, O/V, and V/V). The time course of action was measured mechanomyographically, determining the duration until 25% recovery of the single twitch (DUR25). RESULTS: The onset time of an ID of ORG 9487 was shorter than that of an ID of vecuronium (96 vs 203 sec, P < 0.001). The DUR25 of the ID of ORG 9487 was less than half that of vecuronium (10.7 +/- 2.8 vs 28.8 +/- 6.1 min, P < 0.001). The DUR25 of MD1 and MD2 of ORG 9487 were shorter than those of vecuronium (O/O: 7.3 +/- 2.8 and 8.5 +/- 2.4 min; V/O: 12.7 +/- 3.3 and 11.5 +/- 3.5 min, vs O/V: 16.4 +/- 4.5 and 20.6 +/- 4.7 min; V/V: 18.8 +/- 3.0 and 20.1 +/- 3.8 min, respectively, P < 0.05). AN ID of vecuronium prolonged the DUR25 of MD1 and MD2 of ORG 9487 (P < 0.05). CONCLUSION: ORG 9487 is a muscle relaxant with a shorter duration of action than vecuronium. Maintenance doses of ORG 9487 are also shorter acting than roughly equipotent maintenance doses of vecuronium, irrespective of which relaxant is given initially.

Adolescent↗
PubMed1994

Pharmacokinetics and pharmacokinetic/dynamic relationship of rocuronium bromide in humans.

The existing human pharmacokinetic studies have been reviewed and compared with data derived from animals. The earliest study confirms the similarity of rocuronium to vecuronium with respect to the variables derived from the plasma concentration decay curves and the proportion excreted renally. Other studies led to the conclusion that concurrent administration of volatile anaesthetics did not significantly influence rocuronium pharmacokinetics and that the potentiation must be due to an increased sensitivity of the neuromuscular junction. These studies do not provide an explanation for the clinical observation of a more rapid onset of action. One possible explanation was the finding of a more rapid onset of block in the laryngeal muscles than in the adductor pollicis. However, no pharmacokinetic explanation for this observation has emerged. Alternative concepts need to be modelled. There is a need for comparative pharmacokinetic studies which focus on the period immediately following administration of rocuronium and vecuronium.

Age Factors↗