AIMS: To explore inter- and intra-volunteer variability for the dose of intravenous tyramine eliciting a 20 mmHg increase in systolic blood pressure from baseline (TYR20) and to evaluate potential tachyphylaxis. METHODS:Twelve healthy volunteers received blinded placebo-controlled ascending and descending sequences of intravenous tyramine injections on two separate occasions. The TYR20 was derived by linear interpolation, using three interventions to deal with missing data. RESULTS: Analysis of covariance (ancova) demonstrated no significant difference in TYR20 between sequences, regardless of the missing data methodology applied. Inter-volunteer variability was 2.4-3.4 times larger than within-volunteer variability. No evidence of tachyphylaxis was seen using either the sign test or generalized additive models. CONCLUSIONS: Since inter-volunteer variability was greater than intra-volunteer variability, a crossover study design would be a more efficient study design, and the descending sequence of injections could be omitted since tachyphylaxis was not demonstrated.
RCT Entities:
AIMS: To explore inter- and intra-volunteer variability for the dose of intravenous tyramine eliciting a 20 mmHg increase in systolic blood pressure from baseline (TYR20) and to evaluate potential tachyphylaxis. METHODS: Twelve healthy volunteers received blinded placebo-controlled ascending and descending sequences of intravenous tyramine injections on two separate occasions. The TYR20 was derived by linear interpolation, using three interventions to deal with missing data. RESULTS: Analysis of covariance (ancova) demonstrated no significant difference in TYR20 between sequences, regardless of the missing data methodology applied. Inter-volunteer variability was 2.4-3.4 times larger than within-volunteer variability. No evidence of tachyphylaxis was seen using either the sign test or generalized additive models. CONCLUSIONS: Since inter-volunteer variability was greater than intra-volunteer variability, a crossover study design would be a more efficient study design, and the descending sequence of injections could be omitted since tachyphylaxis was not demonstrated.