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Protocols

VIP protocols in the published literature

StatusNot approved · research probe

PeptideHound Staff · Last editorially reviewed · 16 sources

VIP (vasoactive intestinal peptide) has no recommended dose in the published research, only amounts that trials gave, and none of them is advice. The largest trial, TESICO, gave its synthetic form, aviptadil, as three daily 12-hour infusions stepping up from 600 to 1800 pmol/kg in adults with COVID-19 respiratory failure.

The inhaled form used fixed amounts. A 2008 study gave 20 patients with high lung pressure a single 100 microgram inhalation during heart catheterisation, and a European trial protocol set 67 micrograms three times a day for 10 days. In twelve migraine patients, a research infusion ran at 8 pmol per kilogram per minute.

The older figures are research probes. A 2010 skin study injected 200 picomoles into the forearm, a 1995 scan dose was counted in radioactivity, and dog and cell figures are not converted into human amounts, because no study among these sources validated such a step.

An injection combining VIP with phentolamine was approved for erectile dysfunction in New Zealand and the UK in 2000, and the sources cited on this page give no labelled amount for it. Any approved amount would belong to that combined injection, not to VIP sold alone.

Evidence: Not dosing guidance · the amounts below are study parameters reported as such · intravenous aviptadil amounts from COVID-19 respiratory failure trials, in pmol/kg · inhaled amounts in micrograms from a pulmonary hypertension study and a trial protocol · single research amounts from a skin study, a migraine infusion and a scan · animal and cell figures are not converted

What amounts of VIP did the published studies use?

human RCT

The list is longer than it was, in several kinds of unit, and the units are the first thing to understand. In adults with COVID-19 respiratory failure, the TESICO trial gave aviptadil as a daily 12-h infusion for 3 days, targeting 600 pmol/kg on infusion day 1, 1200 pmol/kg on day 2, and 1800 pmol/kg on day 3.1 A picomole, pmol, is a trillionth of a mole, a count of molecules rather than a weight, and per kilogram means the amount was scaled to body weight. A 2022 case report gave one pregnant patient aviptadil as an hourly rate instead, at 50/100/150 pmol/kg/hr across three 12-hour infusions.8 Inhaled work used micrograms: in 2008, 20 patients with pulmonary hypertension inhaled a single 100-microg dose during a heart catheter test, and a trial protocol planned 67 μg three times a day for 10 days.23 A 2008 migraine study infused 8 pmol kg(-1) min(-1) VIP in 12 patients, a rate per minute rather than a total.4 The older probes were a 200 pmol skin injection in 2010 and a 1995 scan dose of 172 +/- 17 MBq (4.65 +/- 0.5 mCi), counted as radioactivity.56 In dogs, a 1993 study gave graded doses of VIP (1-100 nmol/kg) into an artery, and in nerve cells in a dish a 2016 study found VIP treatment at 1 μM was sufficient to yield maximum protection against manganese.910 Per kilogram, per minute, micrograms and radioactivity cannot be lined up on one scale, and none of these figures is converted into an amount for a person on this page.

Amounts given in the studies described above, in units that cannot be lined up on one scale. Study parameters, not a dosing guide; nothing is converted to a person.
StudyWho or whatRouteAmountUnit counts
TESICO trialAdults with COVID-19 respiratory failureInto a vein, 12 hours a day for 3 days600, then 1200, then 1800 pmol/kgMolecules per kilogram
2022 case reportOne pregnant patient with COVID-19Into a vein, three 12-hour infusions50, then 100, then 150 pmol/kg/hrMolecules per kilogram per hour
2008 lung study20 patients with pulmonary hypertensionInhaled once100 μgWeight
Trial protocolHospital patients at risk of lung failure, plannedInhaled, three times a day for 10 days67 μgWeight
2008 migraine trial12 patients with migraineInto a vein8 pmol/kg/minMolecules per kilogram per minute
2010 skin studyHealthy volunteersInto the skin of the forearm200 pmolMolecules
1995 scanPatients with tumoursInto a vein172 +/- 17 MBq (4.65 +/- 0.5 mCi)Radioactivity
1993 studyDogsInto an artery1-100 nmol/kg, gradedMolecules per kilogram
2016 studyNerve cells in a dishAdded to the solution1 μMSolution strength

Who received those amounts?

human RCT

A wider range of people than before, and very few of them were healthy. The infusion trials took hospitalised adults whose acute hypoxaemic respiratory failure was due to confirmed SARS-CoV-2 infection, most of them already in intensive care.1 The single inhaled dose went to patients with pulmonary hypertension in the middle of a heart catheter procedure.2 The planned inhaled course was written for 132 adult patients hospitalized for COVID-19 and at high risk for ARDS, the severe form of lung failure.3 The stepped hourly infusion went to one woman at 27 weeks of pregnancy, treated outside the trials.8 The older amounts went to 16 healthy volunteers for the skin injections, 18 patients with bowel or hormone-making tumours for the scan, and twelve people with migraine for the research infusion.564 Each of those amounts was fitted to an illness, a setting and a monitoring team, which is what separates a trial parameter from a dose for somebody else.

How was VIP given in the studies?

human RCT

By whatever route the question needed, which is why the routes vary so much. In the volunteer study it went into the skin, so that the reaction stayed in one patch of forearm where it could be measured. For the scan it went into a vein, and after injection of labeled peptide, the lung was the primary site of 123I-VIP uptake.6 A 2001 review reports work in which VIP was administered into the coronary artery or intravenously, in research animals and in humans.11 In dogs, each peptide tested was injected intra-arterially (i.a.) as a single bolus, into the blood supply of the pancreas.9 The aviptadil trials added a slow drip into a vein lasting 12 hours and an inhaled mist.1 A 2022 trial protocol argues that breathing it in achieves a higher concentration in the lung tissue while avoiding the hepatic first-pass metabolism, the breakdown that a swallowed or injected agent can meet in the liver.3 The erectile dysfunction combination goes into the penis itself, and men in a 2025 series were taught to inject it themselves in a nurse-led clinic.12 None of these routes is an injection just under the skin, so the studies behind this page offer no figure at all for that route.

How often was VIP given, and for how long?

human RCT

Over several days in the aviptadil trials, and once in the research probes. TESICO ran its infusion for 12 hours a day on three days running, and the 196-patient trial before it likewise gave 3 days of IV Aviptadil or placebo.113 The European inhaled protocol planned the longest course, three inhalations a day for 10 days on top of standard care.3 The erectile dysfunction series is the only use outside hospital, with men injecting at home and followed for a mean of 13.3 months, and its abstract among these sources gives no frequency.12 One regulatory limit is on record: in 2000 the FDA allowed US studies of the combined injection to run only for a limited duration of 3 months and total number of doses not exceeding three per week.7 That was a ceiling on a trial while a safety question about phentolamine stayed open, and the review does not present it as a schedule for anyone to follow.7 The skin injection, the scan and the migraine infusion were each a single session, so the probes carry no schedule at all.

What does the scan dose actually measure?

human pilot / early trial

Radiation, not peptide, and the difference matters to anybody reading the number. The figure of 172 megabecquerels counts how much radioactivity was injected. A becquerel is one atom decaying per second, so the number describes the iodine label rather than how much VIP was in the syringe. To achieve high-specific activity, 123I-VIP was purified by HPLC, a lab technique for separating molecules.6 High specific activity means a lot of radioactivity packed onto a small amount of peptide, which is the point of a tracer. It is built to be seen on a scanner while doing as little as possible. The study's own dose figure is about radiation, reported as an effective dose of 28 muSv/MBq (104 mrem/mCi).6 So the scan's intravenous figure is a radiation dose rather than a weight of peptide. It cannot be turned into a weight of peptide from the sources cited on this page, and it says nothing about an amount meant to have an effect.

What do the animal and cell amounts tell you?

review

What VIP does at known strengths in tissue, and nothing about what a person should use. In the dog pancreas work, the secretory activity of 30 nmol/kg of PHI corresponded roughly to that of 9 nmol/kg of VIP, a comparison used to rank related peptides against each other.9 PHI is peptide histidine isoleucine, a close chemical cousin of VIP. That experiment used a pancreas kept alive on a blood supply, in preparations of the isolated and blood-perfused dog pancreas, which is far from a whole animal. In heart muscle, the 2001 review reports that in concentrations of 10(-8)-10(-5) mol, VIP augments developed isometric force and increases atrial and ventricular contractility.11 Those are strengths of solution bathing heart tissue, spanning a thousand-fold range. We do not convert any of these figures into a human amount. Scaling from a dog's artery or a dish of cells to a person has not been validated for VIP in the research behind this page, and doing it anyway would be a dose recommendation in disguise.

Did more VIP do more?

in vitro

In tissue and animals, yes, which is what dose-dependent means. The 2001 review states that the VIP peptide combines with its receptor and dose-dependently activates adenylyl cyclase, the enzyme that passes its signal into the cell.11 In the dog study, VIP caused dose-dependent increases in the secretion of pancreatic juice and bicarbonate outputs across its graded range.9 The cell study points to a ceiling, with 1 μM chosen because it was sufficient to yield maximum protection, and these concentrations were adopted in the following experiments.10 Maximum protection at a set strength means adding more did not add more benefit in that dish. Dose-dependence in an organ also cuts both ways for a peptide this active on blood vessels: a larger amount means a larger drop in pressure, as the VIP safety page sets out. The human studies either used one fixed amount or stepped the amount up within the same patients, and neither design can show a dose-response in people.

Is there a VIP dosage chart?

human RCT

Not one that the published research could support, and we do not publish one. A dosage chart lines up amounts against body weight, schedule or purpose. To build one honestly you would need at least two human amounts, given repeatedly, with outcomes measured at each. The research behind this page now holds several human amounts, but each belongs to a different route, illness and form. TESICO stepped its infusion up over three days and judged the outcome only at day 90, so no outcome is tied to any single amount.1 The skin study measured pain intensity on a visual analog scale (VAS), blood flow by laser Doppler flowmetry, visual flare and wheal, which are readings of a local reaction rather than outcomes a chart could be built around.5 A visual analogue scale is a line on which a person marks how much something hurts. Any VIP chart in circulation therefore draws on something other than these studies, whether an animal conversion, a different molecule or a guess. Charts can look authoritative, and that is different from being grounded in measured human doses.

Why is a study amount not a protocol?

human RCT

Because each amount was picked to answer a research question, in a particular body part, for a particular kind of person. The 2010 team chose its skin amount to compare two related peptides, concluding that acute pain and vasomotor responses following intradermal injections of PACAP38 and VIP are primarily mediated by VPAC receptors.5 Vasomotor responses are changes in blood vessel width, and VPAC receptors are the docking sites VIP acts on. The amount was enough to light up those receptors in one patch of skin, and that was its whole job. The scan team's aim was a tracer for localization of tumors expressing receptors for VIP, which needed the smallest amount that would show up.6 A protocol, by contrast, is an amount chosen to change something for the person receiving it, then tested for whether it does. The infusion trials are the first amounts in these sources picked that way, and the largest of them was stopped early on its safety board's advice, for futility.1 An amount tested in very sick patients and found not to work is a trial result, and it does not describe what anybody else would use.

How do you reconstitute a VIP vial, and how many doses are in one?

primary research

None of the studies covered here describes mixing a vial or counting doses in one, because every one of them used material supplied and handled by the research or clinical team. The purification step in the scan work is a reminder of how much handling a research team applied to the peptide before it went into anyone, which is HPLC separation to get a clean, well-characterised material. Checking that material is harder than it looks. A 2014 lab study ran aviptadil through two analytical methods, one revealing 15 detectable impurities and the other two, and none of the impurities detected by CE were observed in LC and vice versa.14 CE and LC are two different separation techniques, and the authors note that peptide quality control is often performed by one single method, which by their figures can miss most of what the other finds.14 The arithmetic of turning a powder into a solution is the same for any peptide and is set out at the reconstitution calculator. It can only be as accurate as the amount printed on the label, and no source behind this page checked a VIP label against what is in the vial, which is the weakest link in the whole calculation.

Is there an approved dose of VIP?

review

One product containing VIP was approved, and the sources cited on this page do not give its labelled amount. A 2001 review records that the injection pairing VIP with phentolamine for erectile dysfunction had been approved in New Zealand by April 2000, and that in October 2000, marketing approval in the UK was granted by the MCA.7 Whatever its label specifies belongs to that combined injection, given for that purpose. It does not transfer to VIP sold on its own, to an inhaled or intravenous form, or to an unlabelled vial. The lung-failure form sits at a different stage. A 2022 review says the formulation named RLF-100 was approved for human trials by FDA in 2001, which is permission to run trials rather than a label with a dose.15 A 2020 review still names synthetically produced vasoactive intestinal peptide among agents for pulmonary arterial hypertension under clinical development.16 So the infusion and inhaled amounts on this page are parameters of particular trials, and none of them is a labelled dose.

What was the starting amount in the studies?

human RCT

Two human records stepped the amount up, and neither is a starting point for anybody else. TESICO began at 600 pmol/kg on the first infusion day and doubled, then tripled, that target on the second and third days.1 The 2022 case report followed the same shape, and its authors describe three successive 12-hour IV infusions of Aviptadil at 50/100/150 pmol/kg/hr escalating doses, per randomized clinical trial NCT04311697.8 Twelve hours at each of those hourly rates matches the TESICO daily targets, so the two reports appear to describe one trial schedule written two ways. In the dog study, the graded design began at the low end of VIP (1-100 nmol/kg) and stepped up, a standard way to map how response grows with amount.9 A stepped design in an intensive-care trial is a way of watching for harm as exposure rises in closely monitored patients. It is not a starting dose for a person outside that setting, and these sources do not say where any other course would begin.

What we don’t know

The gaps in the evidence matter as much as the findings.

  1. 01Which amount, if any, did the work in TESICO. The infusion stepped up over three days, and the outcome was judged only for the course as a whole.
  2. 02What the combination injection's label specifies. The sources cited on this page record its approval and give no amount.
  3. 03How often the erectile dysfunction injection was used. The 308-man series reports follow-up length and effectiveness, with no frequency in its abstract.
  4. 04What the two registered headache trials infused. Both are listed as completed, and their amounts are not given in the sources cited on this page.
  5. 05How long a dose lasts in the blood. The tracer study timed the radioactive label, which is not the same as timing the active peptide.
  6. 06What a vial sold as VIP contains. No source behind this page tested the strength, purity or sterility of such material.
  7. 07How to mix or store it. None of the studies covered here describes reconstituting a vial.

Sources

  1. 1Intravenous 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. doi:10.1016/S2213-2600(23)00147-9human RCT
  2. 2Inhalation of vasoactive intestinal peptide in pulmonary hypertension Eur Respir J 2008. doi:10.1183/09031936.00050008human pilot / early trial
  3. 3Inhaled aviptadil for the possible treatment of COVID-19 in patients at high risk for ARDS: study protocol for a randomized, placebo-controlled, and multicenter trial Trials 2022. doi:10.1186/s13063-022-06723-whuman RCT
  4. 4Vasoactive intestinal peptide causes marked cephalic vasodilation, but does not induce migraine Cephalalgia 2008. doi:10.1111/j.1468-2982.2007.01497.xhuman RCT
  5. 5Cutaneous nociception and neurogenic inflammation evoked by PACAP38 and VIP J Headache Pain 2010. doi:10.1007/s10194-010-0214-3human RCT
  6. 6Vasoactive intestinal peptide receptor scintigraphy J Nucl Med 1995. PMID 7562036human pilot / early trial
  7. 7Aviptadil (Senatek) Curr Opin Investig Drugs 2001. PMID 11566015review
  8. 8Brief Report: Rapid Clinical Recovery From Critical Coronavirus Disease 2019 With Respiratory Failure in a Pregnant Patient Treated With IV Vasoactive Intestinal Peptide Crit Care Explor 2022. doi:10.1097/CCE.0000000000000607human case report
  9. 9Effects of peptide histidine isoleucine on pancreatic exocrine secretion in anaesthetized dogs Clin Exp Pharmacol Physiol 1993. doi:10.1111/j.1440-1681.1993.tb01732.xprimary research
  10. 10Vinpocetine and Vasoactive Intestinal Peptide Attenuate Manganese-Induced Toxicity in NE-4C Cells Biol Trace Elem Res 2016. doi:10.1007/s12011-016-0742-zin vitro
  11. 11Vasoactive intestinal peptide: cardiovascular effects Cardiovasc Res 2001. doi:10.1016/s0008-6363(00)00229-7review
  12. 12Intracavernosal injection of aviptadil and phentolamine for refractory erectile dysfunction J Sex Med 2025. doi:10.1093/jsxmed/qdaf067human pilot / early trial
  13. 13The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in Patients With Critical COVID-19 Respiratory Failure: Results of a 60-Day Randomized Controlled Trial Crit Care Med 2022. doi:10.1097/CCM.0000000000005660human RCT
  14. 14Analytics of the therapeutic peptide aviptadil by sheathless CE-MS and comparison with nanoRP-HPLC-MS J Pharm Biomed Anal 2014. doi:10.1016/j.jpba.2013.09.024primary research
  15. 15Anticipated pharmacological role of Aviptadil on COVID-19 Environ Sci Pollut Res Int 2022. doi:10.1007/s11356-021-17824-5review
  16. 16Pulmonary arterial hypertension specific therapy: The old and the new Pharmacol Ther 2020. doi:10.1016/j.pharmthera.2020.107576review