Table 1 Effect of tolvaptan 15, 30 and 45 mg at baseline, during and after NO-inhibition on the relative changes in GFR (∆51 CrEDTA-clearance), urinary output (∆ UO), free water clearance (Δ CH2O), urinary aquaporin 2 excretion rate (∆ AQP2), fractional excretion of sodium (∆ FENa) and urinary ENaCγ excretion rate (Δ ENaCγ) in a randomized, placebo-controlled, double-blind, crossover, dose–response study of 15 healthy subjects
Periods | Baseline | L-NMMA | Post infusion | p (GLM-within) | ||
|---|---|---|---|---|---|---|
0–90 min | 90–120 min | 120–150 min | 150–180 min | 180–210 min | ||
Δ 51Cr-EDTA-clearance (%) | ||||||
Placebo | - | −5 ± 9 | −1 ± 2 | −5 ± 3 | −3 ± 8 | 0.746 |
Tolvaptan 15 mg | - | −1 ± 7 | 2 ± 4 | −2 ± 5 | 1 ± 5 | |
Tolvaptan 30 mg | - | −5 ± 7 | −3 ± 7 | −3 ± 6 | −4 ± 7 | |
Tolvaptan 45 mg | - | 1 ± 6 | 1 ± 7 | −0.1 ± 7 | −2 ± 7 | |
p (GLM between) | 0.447 | |||||
Δ UO (%) | ||||||
Placebo | - | −49 (−59;−13) | −41 (−49;−5) | −26 (−42;5) | −6 (−27;30) | <0.0001 |
Tolvaptan 15 mg | - | −46 (−57;−34) | −48 (−51;−38) | −45 (−49;−39) | −40 (−47;−26) | |
Tolvaptan 30 mg | - | −40 (−54;−32) | −42 (−55;−34) | −47 (−55;−28) | −39 (−44;−25) | |
Tolvaptan 45 mg | - | −31 (−38;−27) | −42 (−43;−31) | −32 (−41;−26) | −31 (−36;−24) | |
p (GLM between) | 0.002 | |||||
p (ANOVA) | - | 0.217 | 0.078 | 0.001 | <0.0001 | |
Δ CH2O (%) | ||||||
Placebo | - | −57 (−78;−25) | −47 (−63;0) | −31 (−50;14) | −0.5 (−31;37) | <0.0001 |
Tolvaptan 15 mg | - | −53 (−66;−41) | −56 (−60;−39) | −54 (−66;−47) | −51 (−59;−46) | |
Tolvaptan 30 mg | - | −38 (−65;−33) | −46 (−66;−38) | −51 (−63;−35 | −42 (−61;−31) | |
Tolvaptan 45 mg | - | −35 (−49;−30) | −47 (−57;−36) | −33 (−54;−30) | −31 (−46;−26) | |
p (GLM between) | 0.004 | |||||
p (ANOVA) | - | 0.156 | 0.130 | 0.011 | 0.002 | |
Δ AQP2 (%) | ||||||
Placebo | - | −19 (−29;−2) | −21 (−29;−18) | −21 (−28;−12) | −13 (−23;−3) | 0.233 |
Tolvaptan 15 mg | - | −18 (−26;−7) | −13 (−18;−7) | −9 (−18;−2) | −4 (−18;11) | |
Tolvaptan 30 mg | - | −14 (−26;−5) | −19 (−28;−11) | −12 (−24;−2) | −4 (−13;6) | |
Tolvaptan 45 mg | - | −9 (−22;3) | −13 (−22;−2) | −13–23;−4) ( | −2 (−11;6) | |
p (GLM between) | 0.094 | |||||
ΔFENa (%) | ||||||
Placebo | - | −25 (−33;−9) | −33 (−40;−28) | −12 (−30;1) | 4 (−11;25) | 0.433 |
Tolvaptan 15 mg | - | −14 (−28;−3) | −17 (−23;8) | 17 (−5;34) | 46 (0;55) | |
Tolvaptan 30 mg | - | −15 (−18;9) | −10 (−18;9) | 13 (0;19) | 44 (19;61) | |
Tolvaptan 45 mg | - | −12 (−28;4) | −9 (−26;4) | 3 (11;64) | 45 (19;91) | |
p (GLM between) | 0.014 | |||||
p (ANOVA) | - | 0.207 | 0.009 | 0.014 | 0.021 | |
Δ ENaCγ (%) | ||||||
Placebo | - | −11 (−16;−7) | −8 (−20;−3) | −11 (−23;−3) | 2 (−13;18) | |
Tolvaptan 15 mg | - | −9 (−21;−2) | −7 (−15;22) | 5 (−8;13) | 6 (−7;−21) | |
Tolvaptan 30 mg | - | −3 (−13;3) | −5 (−10;5) | 3 (−1; 13) | 8 (−8;19) | |
Tolvaptan 45 mg | - | −13 (−21;3) | −5 (−10;6) | −2 (−8;10) | 13 (−7;18) | |
p (Friedman) | - | 0.564 | 0.392 | 0.008 | 0.031 | |