MEDICAL DISCLAIMER: Educational research guidelines only. Lyophilized peptides are investigational chemical compounds and are NOT approved for human consumption, diagnosis, or therapy. Consult a licensed physician before any research application.
Ulimorelin Dosage Chart, Schedule & Reconstitution Protocol
Quickstart Highlights
Ulimorelin (TZP-101) is an investigational macrocyclic ghrelin-receptor (GHSR-1a) agonist developed as a gastrointestinal prokinetic for diabetic gastroparesis and postoperative ileus, not as a growth-hormone or muscle peptide. It activates ghrelin receptors on enteric neurons to stimulate gut motility and accelerate gastric emptying. In human trials it was given only as a once-daily 30-minute intravenous infusion dosed by body weight, across a 20-600 mcg/kg range, with about 80 mcg/kg the most effective dose for symptom relief (PMID 19298585; 21214610). It is extremely highly protein bound (at least 99% to alpha-1-acid glycoprotein) with a long 10-20 hour half-life (PMID 19432500). Two Phase 3 postoperative-ileus trials failed to beat placebo and it is not approved by the FDA or EMA (PMID 23739196). The subcutaneous reconstitution figures here are an educational measurement reference only.
Reconstitute: Add 1 mL bacteriostatic water → 20 mg/mL concentration.
Typical dose: 20-600 mcg/kg IV infusion (≈80 mcg/kg most-studied); investigational
Easy measuring: At 20 mg/mL, 1 unit = 0.01 mL = 0.2 mg (200 mcg) on a U-100 insulin syringe.
Storage: Lyophilized powder stored frozen at −20 °C; reconstituted solution refrigerated at 2-8 °C and used within about 4 weeks. Protect from light and avoid repeated freeze-thaw cycles.
Half-life: Approximately 10-20 hours (about 13 hours in the first-in-human study), independent of dose.
Route: Intravenous infusion over 30 minutes, dosed by body weight; the subcutaneous model shown here is educational only.
Status: Investigational; not FDA- or EMA-approved; Phase 3 postoperative-ileus trials failed and development was discontinued.
About Ulimorelin
Ulimorelin (TZP-101) is a macrocyclic ghrelin-receptor (GHSR-1a) agonist that was developed as a gastrointestinal prokinetic, not as a bodybuilding or anti-aging peptide [1]. In every published human study it was given as a once-daily 30-minute intravenous infusion dosed by body weight (20-600 mcg/kg); it is not an oral tablet and not a routine subcutaneous injection [2][8]. The subcutaneous reconstitution figures below are an educational measurement reference that mirrors how this site models every compound, and they are not the clinically validated route of administration.\n\nThis guide models a 20 mg vial reconstituted with 1.0 mL of bacteriostatic water (20 mg/mL, i.e. 200 mcg per insulin-syringe unit) so that the weight-based clinical doses map cleanly onto a U-100 syringe for a 70 kg reference subject: roughly 20 mcg/kg ≈ 1,400 mcg (7 units), 40 mcg/kg ≈ 2,800 mcg (14 units), the most-studied 80 mcg/kg ≈ 5,600 mcg (28 units), and 160 mcg/kg ≈ 11,200 mcg (56 units). Understanding the correct Ulimorelin dosage means working in micrograms per kilogram of body weight rather than a single flat dose.\n\nFrequency: Once daily, delivered as a 30-minute IV infusion in the clinical setting (educational model: one subcutaneous dose per day). Ulimorelin is investigational, is not FDA- or EMA-approved, and everything here is for educational purposes only, not medical advice.
Quick Protocol Navigation
Reconstitution Instruction & Mixing Step-by-Step
Lyophilized powder must be reconstituted carefully. Agitating peptide chains can shear disulfide bonds and render the peptide biologically inert.
Draw 1.0 mL of bacteriostatic water into a sterile syringe.
Inject the water slowly down the inner glass wall of the 20 mg Ulimorelin vial; do not spray it directly onto the powder and do not shake the vial.
Swirl gently until the powder is fully dissolved and the solution is clear; this yields a 20 mg/mL concentration, or 200 mcg per insulin-syringe unit (each unit = 0.01 mL).
Store refrigerated at 2-8 °C and draw the prescribed units per dose for a 70 kg reference subject: 7 units ≈ 20 mcg/kg, 14 units ≈ 40 mcg/kg, 28 units ≈ the 80 mcg/kg target, 56 units ≈ 160 mcg/kg.
Educational note: Ulimorelin is clinically given as a 30-minute INTRAVENOUS infusion in a monitored hospital setting; these subcutaneous reconstitution figures are a measurement reference only and are not a validated route of self-administration.
Interactive Ulimorelin Syringe Calculator
Currently visualizing the 20 mg vial reconstituted with 1 mL bacteriostatic water. Adjust the target dose to dynamically render syringe units.
Reconstitution Calculation: 20mg dry powder in 1mL water yields 20.00 mg/mL. To evaluate a 250mcg dose, pull to 1.3 units (1 syringe ticks).
U-100 Syringe Representation
Educational reference visual. Assumes standard U-100 insulin syringe where 1.0 mL volume = 100 units.
Titration & Dose Escalation Schedules
| Phase | Dose per injection | Units (per injection) |
|---|---|---|
| Initiation / Phase I tolerability (~20 mcg/kg, 70 kg) | 1400 mcg (1.4 mg) | 7 units (0.07 mL) |
| Low gastroparesis dose (~40 mcg/kg) | 2800 mcg (2.8 mg) | 14 units (0.14 mL) |
| Target efficacy dose (~80 mcg/kg, most-studied) | 5600 mcg (5.6 mg) | 28 units (0.28 mL) |
| Upper dose-ranging (~160 mcg/kg) | 11200 mcg (11.2 mg) | 56 units (0.56 mL) |
Administration guidelines: Refer to guidelines | 1 mL Reconstitution
Research Supplies Quantity Planner
Scientific mathematical planning of syringes, bacteriostatic water and dry vials needed for extended research blocks using the 20 mg vial.
Peptide Vials (Ulimorelin, 20 mg each):
- checkAt the ~80 mcg/kg target dose (about 5.6 mg/day for a 70 kg subject), an 8-week daily course needs about 16 vials.
- checkA 12-week course needs about 24 vials.
- checkA 16-week course needs about 32 vials.
- checkLower mcg/kg doses use proportionally fewer vials (for example a ~40 mcg/kg dose halves the requirement).
Insulin Syringes (U-100):
- checkOne sterile U-100 syringe per daily dose: about 56 over an 8-week course.
- checkAbout 84 syringes over a 12-week course.
- checkAbout 112 syringes over a 16-week course.
- checkAdd a few extra syringes for reconstitution draws and round up for spares.
Bacteriostatic Water (30 mL bottles): Use 1.0 mL per vial for reconstitution.
- check8-week course (about 16 vials, ~16 mL): one 30 mL bottle.
- check12-week course (about 24 vials, ~24 mL): one 30 mL bottle.
- check16-week course (about 32 vials, ~32 mL): two 30 mL bottles.
- checkDiscard any reconstituted solution not used within about 4 weeks of refrigeration.
Alcohol Swabs: clean the vial stopper and the injection site before each use.
- checkAbout 120 swabs over an 8-week course (roughly two per dose).
- checkAbout 170 swabs over a 12-week course.
- checkAbout 230 swabs over a 16-week course.
- checkKeep a surplus on hand for vial reconstitution and spills.
Mechanism of Action (MOA)
Ulimorelin is a synthetic macrocyclic peptidomimetic, a constrained and modified cyclic peptide with the formula C30H39FN4O4 and a molecular weight of about 538 Da (CAS 842131-33-3), designed by Tranzyme Pharma medicinal chemists to act as a potent, selective agonist of the ghrelin/growth hormone secretagogue receptor type 1a (GHSR-1a) [1]. The macrocyclic ring locks the molecule into a bioactive conformation, raising receptor potency while conferring the metabolic stability and drug-like pharmacokinetics that simple linear peptides lack [1]. Like endogenous ghrelin, it engages GHSR-1a on enteric neurons and within the gut, where receptor activation stimulates gastrointestinal smooth-muscle contractility and accelerates gastric emptying and colonic transit, the prokinetic effect that motivated its development for gastroparesis and postoperative ileus [4][5].\n\nUnlike the ghrelin mimetics used for growth-hormone goals, ulimorelin was selected for a peripheral, prokinetic profile; in rodents it had little effect on growth-hormone release, although in humans it does produce a transient, dose-related rise in growth hormone and IGF-1 because GHSR-1a is also expressed on pituitary somatotrophs [1][9]. It was also observed to inhibit alpha-1-adrenergic vasoconstriction of rat arteries in vitro, but clinically meaningful blood-pressure effects were not seen in human trials [9].\n\nPharmacokinetics: Ulimorelin is administered as a 30-minute intravenous infusion, so bioavailability is complete by definition and oral or subcutaneous absorption is not the clinical route. First-in-human work showed low systemic clearance (about 7 mL/h/kg), a small volume of distribution (about 100-180 mL/kg), and a long elimination half-life of roughly 13 hours in the Phase I study and 10-20 hours across later studies, independent of dose [2][3]. Plasma exposure rose less than dose-proportionally over the 20-600 mcg/kg range [2]. The compound is extremely highly bound to plasma proteins, principally alpha-1-acid glycoprotein (at least 99% bound between 5 and 15 micromol/L), so the small free fraction, not the total plasma concentration, drives pharmacodynamics and should anchor any safety assessment [3]. The long half-life and once-daily clinical infusion schedule are consistent with this slow clearance [2].\n\nDownstream, pharmacodynamic activity at the receptor was detectable at doses as low as 40 mcg/kg, and 80 mcg/kg produced the clearest acceleration of gastric emptying and the strongest symptom relief in diabetic gastroparesis [4][5][6]. Higher doses (160 and 480 mcg/kg) were carried into the postoperative-ileus program [7][8].\n\nThe real-world route is intravenous infusion; the subcutaneous reconstitution scheme on this page is an educational measurement convention used across this site, not a clinically validated delivery method. Ulimorelin remains investigational and is not approved by any major regulator [8][9].
Clinical Trial Efficacy Highlights
- starHoveyda and colleagues (2011, Journal of Medicinal Chemistry) described the discovery and optimization of ulimorelin (TZP-101), a macrocyclic peptidomimetic engineered for high GHSR-1a potency, metabolic stability, and drug-like pharmacokinetics, taking it from a screening hit to a clinical candidate [1].
- starLasseter and colleagues (2008, Journal of Clinical Pharmacology) ran the first-in-human Phase I study: single 30-minute IV infusions of 20-600 mcg/kg in healthy volunteers were generally well tolerated, with low clearance (~7 mL/h/kg), a small volume of distribution (~114 mL/kg), and a half-life of about 13 hours independent of dose, while receptor pharmacodynamic activity was detectable at doses as low as 40 mcg/kg [2].
- starWargin and colleagues (2009, Clinical Drug Investigation) combined two randomized double-blind studies with a binding-profile study and showed TZP-101 was at least 99% bound to plasma proteins (mainly alpha-1-acid glycoprotein) between 5 and 15 micromol/L, with a half-life of 10-20 hours, concluding that the free drug fraction rather than total concentration should anchor exposure-safety judgments [3].
- starEjskjaer and colleagues (2009, Alimentary Pharmacology & Therapeutics) found that in adults with diabetes and symptomatic gastroparesis, single IV infusions of TZP-101 significantly accelerated gastric emptying versus placebo and improved upper-gastrointestinal symptoms [4].
- starEjskjaer and colleagues (2010, Neurogastroenterology & Motility) ran a randomized placebo-controlled study giving four consecutive daily 30-minute infusions of 20-600 mcg/kg (n=57) versus placebo (n=19) in diabetic gastroparesis; all doses were well tolerated and the 80 mcg/kg dose was the most effective for symptom relief [5].
- starWo and colleagues (2011, Alimentary Pharmacology & Therapeutics) analyzed a subset of 23 diabetic gastroparesis patients with severe baseline nausea and vomiting and reported that 80 mcg/kg reduced the Gastroparesis Cardinal Symptom Index nausea/vomiting subscale by -3.82 (P=0.011) and cut vomiting days versus placebo, with benefit maintained at 30-day follow-up [6].
- starA Phase 2 postoperative-ileus trial after partial colectomy (2010, Diseases of the Colon & Rectum) adaptively randomized adults to IV TZP-101 or placebo started within an hour of surgical closure and daily thereafter, and showed encouraging signals on time to first bowel movement and gastrointestinal recovery that justified moving to Phase 3 [7].
- starShaw and colleagues (2013, Diseases of the Colon & Rectum) reported the two pivotal Phase 3 trials (USES 007, n=332; USES 008, n=330) testing 160 and 480 mcg/kg once-daily infusions after partial bowel resection; the composite primary endpoint of first bowel movement plus solid-food tolerance did not differ from placebo, ending the program and leaving ulimorelin unapproved [8].
Side Effects & Tolerability Profile
Clinical subjects transiently report mild side effects. Slowly escalating the titration dose represents the single most effective intervention to limit side effects.
- warningIn the Phase I first-in-human study, ulimorelin was generally well tolerated, with only isolated mild events such as headache, lower abdominal pain, diarrhea, and dizziness reported after single IV infusions [2].
- warningAt the highest infused dose (600 mcg/kg), two healthy volunteers developed transient, self-limited bradycardia, which is why trials used continuous cardiac monitoring during and after infusion [2].
- warningAs an intravenous-infusion drug, infusion-site reactions and effects related to rapid administration are the route-specific concerns; the subcutaneous model on this page is educational and was never a clinical route [2][9].
- warningBecause GHSR-1a is expressed on pituitary somatotrophs, transient rises in growth hormone and IGF-1 can occur even though the molecule was selected for a peripheral prokinetic profile [1][9].
- warningExtremely high protein binding (at least 99% to alpha-1-acid glycoprotein) means the small free fraction drives the effect; conditions or co-medications that change alpha-1-acid glycoprotein levels could in theory alter active exposure [3].
- warningGhrelin-pathway prokinetics can theoretically influence appetite, glucose handling, and gastric motility; long-term human safety data are limited because development was stopped after Phase 3 [8].
- warningCaution context: ulimorelin was only ever studied in supervised hospital settings with cardiac monitoring; it is not intended for self-administration and has no established outpatient safety profile.
- warningRegulatory and research status: Ulimorelin is NOT approved by the FDA or EMA; two Phase 3 postoperative-ileus trials failed to beat placebo and development was discontinued, so it remains investigational and for research or educational use only [8][9].
Subcutaneous Injection Technique
Most research peptides require subcutaneous injection into fatty tissue. Never inject directly into a blood vessel or deep muscle tissue unless clinically detailed.
1. Site Selection
Common locations include the abdomen (2 inches from navel), outer upper arms, or thighs.
2. Sanitization
Thoroughly clean the selected site, stopper and vial top using 70% isopropyl alcohol prep swabs.
3. Angle & Push
Pinch the skin and insert the needle at a 45 to 90-degree angle. Depress plunger smoothly.
4. Site Rotation
Rotate injection sites continuously to avoid lipodystrophy or tissue scarring.
Frequently Asked Questions
What is the typical Ulimorelin dosage?expand_more
In human trials the typical Ulimorelin dosage was a once-daily 30-minute intravenous infusion dosed by body weight, studied across a 20-600 mcg/kg range. About 80 mcg/kg was the most effective dose for relieving diabetic gastroparesis symptoms and accelerating gastric emptying, while the Phase 3 postoperative-ileus trials used 160 and 480 mcg/kg. There is no established subcutaneous or oral dose; the per-injection micrograms shown here are an educational conversion for a 70 kg reference subject.
Is Ulimorelin FDA approved?expand_more
No. Ulimorelin (TZP-101) is investigational and is not approved by the FDA or the EMA for any indication. Two pivotal Phase 3 trials in postoperative ileus (USES 007 and USES 008) failed to separate from placebo on the primary endpoint, and the development program was discontinued. It is presented here for educational and research reference only, not as an approved medicine.
What is the half-life of Ulimorelin?expand_more
Ulimorelin has a relatively long elimination half-life, reported as about 13 hours in the first-in-human Phase I study and 10-20 hours across later studies, and it was independent of dose. This long half-life reflects low systemic clearance (about 7 mL/h/kg), a small volume of distribution, and very high plasma protein binding (at least 99% to alpha-1-acid glycoprotein). The once-daily clinical infusion schedule is consistent with this slow clearance.
How is Ulimorelin administered and reconstituted?expand_more
Clinically, Ulimorelin is given only as a 30-minute intravenous infusion in a monitored hospital setting, never by self-injection. The reconstitution steps on this page are an educational measurement reference: draw 1.0 mL of bacteriostatic water into a 20 mg vial to make a 20 mg/mL solution (200 mcg per U-100 syringe unit), swirl gently until clear, refrigerate, and draw the units corresponding to the desired mcg/kg dose for the reference body weight.
Can Ulimorelin be stacked with other peptides?expand_more
There is no clinical evidence for stacking Ulimorelin with other peptides. It was developed and tested as a standalone hospital-administered prokinetic infusion for gastroparesis and postoperative ileus, not as a performance or anti-aging compound, and its development was halted after Phase 3. Because it is investigational with no outpatient safety data, combining it with other agents is not supported by any published research.
Related Guides & Tools
Step-by-step references for reconstituting, measuring, and storing Ulimorelin, plus the universal dosing calculator.
Academic References & Study Citations
Hoveyda HR, Marsault E, Gagnon R, et al. Optimization of the Potency and Pharmacokinetic Properties of a Macrocyclic Ghrelin Receptor Agonist (Part I): Development of Ulimorelin (TZP-101) from Hit to Clinic. J Med Chem. 2011;54(24):8305-8320. View Scientific Paper →
Lasseter KC, Shaughnessy L, Cummings D, et al. Ghrelin Agonist (TZP-101): Safety, Pharmacokinetics and Pharmacodynamic Evaluation in Healthy Volunteers: A Phase I, First-in-Human Study. J Clin Pharmacol. 2008;48(2):193-202. View Scientific Paper →
Wargin W, Thomas H, Clohs L, St-Louis C, Ejskjaer N, Gutierrez M, Shaughnessy L, Kosutic G. Contribution of protein binding to the pharmacokinetics of the ghrelin receptor agonist TZP-101 in healthy volunteers and adults with symptomatic gastroparesis. Clin Drug Investig. 2009;29(6):409-418. PMID 19432500. View Scientific Paper →
Ejskjaer N, et al. Ghrelin receptor agonist (TZP-101) accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis. Aliment Pharmacol Ther. 2009. PMID 19298585. View Scientific Paper →
Ejskjaer N, et al. Safety and efficacy of ghrelin agonist TZP-101 in relieving symptoms in patients with diabetic gastroparesis: a randomized, placebo-controlled study. Neurogastroenterol Motil. 2010. View Scientific Paper →
Wo JM, Ejskjaer N, Hellström PM, Malik RA, Pezzullo JC, Shaughnessy L, Charlton P, Kosutic G, McCallum RW. Randomised clinical trial: ghrelin agonist TZP-101 relieves gastroparesis associated with severe nausea and vomiting. Aliment Pharmacol Ther. 2011;33(6):679-688. PMID 21214610. View Scientific Paper →
The ghrelin agonist TZP-101 for management of postoperative ileus after partial colectomy: a randomized, dose-ranging, placebo-controlled clinical trial. Dis Colon Rectum. 2010. PMID 20087086. View Scientific Paper →
Shaw M, Pediconi C, McVey D, Mondou E, Quinn J, Chamblin B, Rousseau F. Safety and efficacy of ulimorelin administered postoperatively to accelerate recovery of gastrointestinal motility following partial bowel resection: results of two randomized, placebo-controlled phase 3 trials. Dis Colon Rectum. 2013;56(7):888-897. PMID 23739196. View Scientific Paper →
Ulimorelin. Wikipedia (drug class, structure, GHSR-1a mechanism, and Phase 3 postoperative-ileus outcome). View Scientific Paper →
ClinicalTrials.gov. Study to Evaluate the Safety of Post-Operative TZP-101 (IV Ulimorelin) After Partial Bowel Resection (NCT01710982). View Scientific Paper →