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.
VIP Dosage Chart, Schedule & Reconstitution Protocol
Quickstart Highlights
VIP (vasoactive intestinal peptide; synthetic form aviptadil) is a 28-amino-acid neuropeptide that activates the VPAC1 and VPAC2 receptors, raising cAMP to drive vasodilation, bronchodilation, and a strongly anti-inflammatory, regulatory-T-cell-favoring immune shift (PMID 22461771-era VPAC pharmacology; PMID 730072 for kinetics). Because native VIP is cleaved within 1-2 minutes by DPP-4 and neutral endopeptidase, it cannot be dosed orally or as a single shot; real-world use is a compounded intranasal spray at 50 mcg per actuation 1-4 times daily in the Shoemaker CIRS protocol, inhaled aviptadil for pulmonary hypertension (PMID 12727925, 18978135), or escalating IV aviptadil for respiratory failure. The largest randomized trial, TESICO (PMID 37348524), found no survival benefit in COVID-19. VIP is not FDA- or EMA-approved; the subcutaneous reconstitution figures here are an educational measurement reference only.
Reconstitute: Add 2 mL bacteriostatic water → 2.5 mg/mL concentration.
Typical dose: 50 mcg per dose, 1-4 times daily (intranasal in practice)
Easy measuring: At 2.5 mg/mL, 1 unit = 0.01 mL = 0.0250 mg (25 mcg) on a U-100 insulin syringe.
Storage: Lyophilized powder stored frozen at −20 °C and protected from light. Once reconstituted, VIP is fragile: keep refrigerated at 2-8 °C and use within roughly 30 days; compounded intranasal VIP sprays are typically assigned a 30-60 day refrigerated beyond-use date. Do not freeze the reconstituted solution and avoid repeated warming.
Half-life: Roughly 1-2 minutes in plasma; rapidly cleaved by DPP-4 and neutral endopeptidase, so frequent dosing or continuous infusion is required.
Route: Real-world: intranasal 50 mcg spray (CIRS) or IV/inhaled aviptadil. The subcutaneous reconstitution on this page is an educational model only.
Status: Not FDA- or EMA-approved. Aviptadil is investigational with orphan designations; CIRS use is off-label compounded. Research/educational use only.
About VIP
VIP (vasoactive intestinal peptide) is a 28-amino-acid neuropeptide that activates the VPAC1 and VPAC2 receptors and raises cAMP, producing vasodilation, bronchodilation, and a strong anti-inflammatory, regulatory-T-cell-favoring immune signal [2][3]. Clinically it is NOT given subcutaneously: in the Shoemaker CIRS protocol it is a compounded intranasal spray delivering 50 mcg per actuation used one to four times daily [8], and the synthetic version aviptadil has been delivered by inhalation for pulmonary hypertension [4][5] and by intravenous infusion for respiratory failure [6]. The subcutaneous reconstitution figures below are an educational measurement reference only, mirroring how this site models every compound on a common unit scale.\n\nThis guide models a 5 mg VIP vial reconstituted with 2 mL of bacteriostatic water (2.5 mg/mL, i.e. 25 mcg per insulin-syringe unit) so the 50 mcg unit dose maps cleanly to 2 units on a U-100 syringe. Titration in VIP protocols is by frequency, not by raising the per-dose amount: many CIRS patients begin at 50 mcg once daily to confirm tolerance, then build toward 50 mcg up to four times daily.\n\nFrequency: Up to four times daily (modeled here as subcutaneous; intranasal 50 mcg per spray in real-world CIRS use). Because native VIP has a ~1-2 minute half-life [1], frequent dosing is intrinsic to the protocol. VIP/aviptadil is not FDA- or EMA-approved and is presented here for educational purposes only.
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 2 mL of bacteriostatic water into a sterile syringe.
Inject the water slowly down the inner glass wall of the 5 mg VIP vial; never aim the stream directly at the lyophilized pellet and do not shake.
Swirl or roll the vial gently until the solution is completely clear; the result is 2.5 mg/mL, which equals 25 mcg per U-100 insulin-syringe unit.
Store refrigerated at 2-8 °C and draw 2 units (50 mcg) per dose; repeat per the chosen frequency (for example 2 units up to four times daily). Use within roughly 30 days.
Educational note: clinically VIP is delivered INTRANASALLY (50 mcg per spray) or, as aviptadil, by IV infusion — these subcutaneous figures are a measurement reference only. For subcutaneous educational modeling, inject slowly into a rotated site, then wait a few seconds before withdrawing the needle.
Interactive VIP Syringe Calculator
Currently visualizing the 5 mg vial reconstituted with 2 mL bacteriostatic water. Adjust the target dose to dynamically render syringe units.
Reconstitution Calculation: 5mg dry powder in 2mL water yields 2.50 mg/mL. To evaluate a 250mcg dose, pull to 10.0 units (10 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) |
|---|---|---|
| CIRS initiation (once daily, ~1-2 weeks to confirm tolerance) | 50 mcg | 2 units (0.02 mL) |
| CIRS maintenance (same 50 mcg dose, titrated up to 4× daily) | 50 mcg | 2 units (0.02 mL) |
| Pulmonary research reference (single inhaled aviptadil dose) | 100 mcg | 4 units (0.04 mL) |
Administration guidelines: Refer to guidelines | 2 mL Reconstitution
Research Supplies Quantity Planner
Scientific mathematical planning of syringes, bacteriostatic water and dry vials needed for extended research blocks using the 5 mg vial.
Peptide Vials (VIP, 5 mg each):
- checkAt 50 mcg × 4 doses/day the model uses about 1.4 mg per week.
- check8-week course: ~11.2 mg used — plan ~3 vials.
- check12-week course: ~16.8 mg used — plan ~4 vials.
- check16-week course: ~22.4 mg used — plan ~5 vials, and keep one spare to cover the ~30-day reconstituted stability limit.
Insulin Syringes (U-100):
- checkOne 0.3-0.5 mL U-100 syringe per dose; at 4 doses/day that is 28 per week (each 50 mcg dose = 2 units).
- check8 weeks: ~224 syringes.
- check12 weeks: ~336 syringes.
- check16 weeks: ~448 syringes.
Bacteriostatic Water (30 mL bottles): Use 2 mL per vial for reconstitution.
- checkEach 5 mg vial is reconstituted with 2 mL, giving 2.5 mg/mL (25 mcg per unit).
- check8-16 week courses use only ~6-10 mL total — a single 30 mL bottle covers every course.
- checkDiscard an opened bottle after about 28 days or per the manufacturer label.
Alcohol Swabs: clean the vial stopper and the injection site before every dose.
- checkAbout 2 swabs per dose (vial top plus skin) ≈ 56 per week.
- check8 weeks: ~450 swabs (2-3 boxes of 200).
- check12 weeks: ~670 swabs (about 4 boxes of 200).
- check16 weeks: ~900 swabs (about 5 boxes of 200).
Mechanism of Action (MOA)
VIP is a 28-amino-acid neuropeptide of the secretin/glucagon superfamily, encoded by the VIP gene on chromosome 6 and released from enteric, autonomic, and central neurons where it acts mainly as a paracrine signal rather than a circulating hormone [1]. It binds two class II G-protein-coupled receptors, VPAC1 and VPAC2, with nanomolar affinity. Both couple preferentially to Gαs, activating adenylyl cyclase, raising intracellular cAMP, and engaging protein kinase A (with secondary phospholipase C/calcium signaling); the cAMP/PKA axis is the dominant route for VIP's downstream effects [2]. VPAC1 predominates on T cells, macrophages, and pulmonary alveolar type II cells, while VPAC2 concentrates in vascular and airway smooth muscle, enteric neurons, and the suprachiasmatic nucleus, where VIP synchronizes circadian rhythm [2].\n\nFunctionally, VIP is a potent vasodilator and bronchodilator and a broad immune modulator. Through VPAC1 and the cAMP/PKA pathway it suppresses pro-inflammatory mediators such as TNF-α, IL-6, and IL-12, promotes IL-10, biases T cells away from Th1 toward Th2, and induces regulatory T cells and tolerogenic dendritic cells [3]. In the lung, aviptadil binds VPAC1 on type II alveolar cells, supports surfactant production, blocks caspase-3-mediated apoptosis, and dampens cytokine release, which is the rationale for testing it in acute respiratory distress and pulmonary hypertension [4][5][7].\n\nPharmacokinetics dominate how VIP is dosed. Native VIP has an exceptionally short circulating half-life of roughly 1-2 minutes; classic human infusion studies measured a disappearance half-time near one minute, with a metabolic clearance around 9 mL/kg/min, because plasma and endothelial DPP-4 and neutral endopeptidase rapidly cleave the peptide [1]. There is no meaningful oral bioavailability. Consequently, real-world delivery uses routes that bypass this constraint: a compounded intranasal spray (50 mcg per actuation, 1-4 times daily) for direct mucosal and CNS-adjacent exposure in the Shoemaker CIRS protocol [8][9]; aerosolized aviptadil for selective pulmonary vasodilation in pulmonary arterial hypertension [4][5]; and continuous or escalating intravenous infusion of aviptadil over successive days for COVID-19 respiratory failure [6][7]. Stabilized analogs (for example elastin-fused or VPAC2-selective agonists) are being engineered specifically to extend this half-life.\n\nThe subcutaneous reconstitution scheme on this page is an educational measurement convention used across this site, not a clinically validated delivery method for VIP. VIP/aviptadil is not approved by the FDA or EMA, and its CIRS use rests on open-label, observational data from a niche literature [6][8].
Clinical Trial Efficacy Highlights
- starPetkov and colleagues (2003, Journal of Clinical Investigation) found primary pulmonary hypertension patients were deficient in VIP in serum and lung tissue, and that inhaled VIP substitution (about 200 mcg/day for 12-24 weeks) lowered mean pulmonary artery pressure, improved cardiac output and mixed venous oxygen saturation, and increased six-minute walk distance in a small open-label cohort, without documented adverse effects [4].
- starLeuchte and colleagues (2008, European Respiratory Journal) gave a single 100 mcg inhaled dose of aviptadil to 20 patients with chronic pulmonary hypertension during right-heart catheterization and observed a small, temporary but statistically significant selective pulmonary vasodilation with improved stroke volume and mixed venous oxygen saturation, while noting the effect was modest and short-lived [5].
- starThe TESICO trial (Brown et al., 2023, Lancet Respiratory Medicine), a large randomized, placebo-controlled study of intravenous aviptadil in COVID-19-associated acute hypoxaemic respiratory failure, found NO significant clinical benefit: mortality was 37% with aviptadil versus 36% with placebo, and the data safety board stopped the aviptadil analysis for futility — the most rigorous VIP efficacy evidence to date and a negative result [6].
- starEarly uncontrolled and case-control reports during the pandemic (summarized by Mukherjee et al., 2021, Environmental Science and Pollution Research) suggested aviptadil might protect type II alveolar cells and reduce cytokine-driven lung injury, but these signals were not confirmed once the definitive randomized trial reported [6][7].
- starShoemaker, House and Ryan (2013, Health) reported in an open-label series that intranasal VIP (50 mcg per spray) in CIRS patients was associated with normalization of inflammatory biomarkers such as TGF-β1, MMP-9, C4a, and VEGF and improvement in visual contrast sensitivity; this is observational, single-investigator evidence from a low-impact journal and has not been independently replicated in controlled trials [8].
- starShoemaker and colleagues (2017, Internal Medicine Review) used sequential NeuroQuant MRI volumetrics to report that intranasal VIP was associated with restoration of volume in multiple atrophic grey-matter nuclei in CIRS patients, again as uncontrolled observational data that requires confirmation [9].
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.
- warningSystemic vasodilation can cause hypotension, facial flushing, warmth, headache, and reflex tachycardia or palpitations; these are most relevant with intravenous aviptadil and were among the known effects managed in the TESICO trial [6].
- warningDiarrhea is a recognized dose-limiting effect of VIP, consistent with its role in stimulating intestinal water and electrolyte secretion (the peptide was originally isolated from gut and is the mediator in VIPoma-associated watery diarrhea) [6].
- warningIntranasal VIP can cause local nasal irritation, rhinorrhea, stinging, or transient lightheadedness shortly after spraying; the CIRS literature also describes early symptom flares when VIP is started before other steps are completed [8].
- warningIn the Shoemaker protocol, VIP is intended as a final step after MARCoNS nasal colonization is cleared and visual contrast sensitivity is normalized; using it too early is reported to worsen symptoms, underscoring that it is not a stand-alone therapy [8][9].
- warningCaution or avoidance is advised in people with low blood pressure, recent cardiac events, significant arrhythmia, or who take other vasodilators/antihypertensives, given additive blood-pressure and heart-rate effects; safety in pregnancy and lactation is not established.
- warningThe ~1-2 minute plasma half-life means systemic exposure from any single dose is brief, but it also requires frequent dosing or infusion; intravenous administration warrants hemodynamic monitoring [1][6].
- warningDefinitive randomized evidence (TESICO) showed no survival benefit in COVID-19 respiratory failure, so claimed broad therapeutic benefits beyond the studied settings are not supported by controlled trials [6].
- warningRegulatory/research status: VIP/aviptadil is NOT approved by the FDA or EMA for any indication; aviptadil holds only orphan-drug designations, CIRS use is off-label compounded therapy, and long-term human safety data are limited — treat this as research/educational information only.
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 VIP dosage?expand_more
The most cited VIP dosage is 50 mcg per intranasal spray, used one to four times daily, from Ritchie Shoemaker's open-label CIRS protocol; titration is by frequency rather than by raising the per-dose amount. As the synthetic drug aviptadil, VIP has been inhaled at roughly 100-200 mcg/day for pulmonary hypertension and given by escalating intravenous infusion for respiratory failure. The 50 mcg per dose modeled on this page (2 units of a 5 mg vial reconstituted in 2 mL) is an educational subcutaneous reference, not a prescription.
Is VIP FDA approved?expand_more
No. VIP and its synthetic form aviptadil (RLF-100/ZYESAMI) are not approved by the FDA or EMA for any indication. Aviptadil received orphan-drug designations for ARDS and pulmonary hypertension and was studied under emergency/investigational pathways for COVID-19, but the definitive randomized TESICO trial found no mortality benefit. Intranasal VIP for CIRS is off-label, compounded therapy supported only by open-label, observational data. Everything here is educational and not medical advice.
How do you reconstitute VIP for the educational protocol?expand_more
For VIP reconstitution in this model, draw 2 mL of bacteriostatic water and add it slowly down the wall of a 5 mg vial, then swirl gently until clear. That yields 2.5 mg/mL, or 25 mcg per U-100 insulin-syringe unit, so a 50 mcg dose is 2 units. Refrigerate at 2-8 °C and use within about 30 days. In real-world use VIP is intranasal or intravenous, so this is purely a measurement reference.
What is the half life of VIP?expand_more
Native VIP has a very short plasma half-life of roughly 1-2 minutes; classic human infusion studies measured a disappearance half-time near one minute because DPP-4 and neutral endopeptidase rapidly cleave the peptide. That brevity is why therapeutic use depends on frequent intranasal dosing or continuous IV infusion rather than a single injection, and why longer-acting stabilized analogs are being developed.
What are the main VIP side effects, and is it safe?expand_more
Common VIP side effects relate to its vasodilator and gut-secretory actions: hypotension, flushing, headache, palpitations, and diarrhea, mainly with intravenous aviptadil; intranasal use can cause local nasal irritation or transient lightheadedness. It should be used cautiously with low blood pressure, recent cardiac events, or other vasodilators, and is not established as safe in pregnancy. Because it is investigational and not regulator-approved, long-term safety is not fully characterized.
Related Guides & Tools
Step-by-step references for reconstituting, measuring, and storing VIP, plus the universal dosing calculator.
Academic References & Study Citations
Domschke S, Domschke W, Bloom SR, Mitznegg P, Mitchell SJ, Lux G, Strunz U. Vasoactive intestinal peptide in man: pharmacokinetics, metabolic and circulatory effects. Gut. 1978;19(11):1049-1053. View Scientific Paper →
Couvineau A, Laburthe M. Mechanisms involved in VPAC receptors activation and regulation: lessons from pharmacological and mutagenesis studies. Front Endocrinol (Lausanne). 2012;3:129. View Scientific Paper →
Delgado M, Ganea D. Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functions. Amino Acids. 2013;45(1):25-39. View Scientific Paper →
Petkov V, Mosgoeller W, Ziesche R, et al. Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension. J Clin Invest. 2003;111(9):1339-1346. View Scientific Paper →
Leuchte HH, Baezner C, Baumgartner RA, et al. Inhalation of vasoactive intestinal peptide in pulmonary hypertension. Eur Respir J. 2008;32(5):1289-1294. View Scientific Paper →
Brown SM, et al (TESICO/ACTIV-3b). Intravenous aviptadil and remdesivir for treatment of COVID-19-associated hypoxaemic respiratory failure in the USA (TESICO): a randomised, placebo-controlled trial. Lancet Respir Med. 2023;11(9):791-803. View Scientific Paper →
Mukherjee T, Behl T, Sharma S, et al. Anticipated pharmacological role of Aviptadil on COVID-19. Environ Sci Pollut Res Int. 2021;29(6):8109-8125. View Scientific Paper →
Shoemaker RC, House D, Ryan JC. Vasoactive intestinal polypeptide (VIP) corrects chronic inflammatory response syndrome (CIRS) acquired following exposure to water-damaged buildings. Health. 2013;5(3A):396-401. View Scientific Paper →
Shoemaker R, Katz D, Ackerley M, et al. Intranasal VIP safely restores volume to multiple grey matter nuclei in patients with CIRS. Internal Medicine Review. 2017;3(4):1-14. View Scientific Paper →